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“Life is the ultimate chemist, crafting intricate molecules with precision and elegance. As we strive to harness its power, we are reminded of the words of the renowned biochemist, Dr. Frances Arnold: ‘Life is a chemical synthesis, and we are just beginning to understand the rules of the game.’ In this review, we delve into the burgeoning field of synthetic biology, where the boundaries between nature and chemistry are being pushed to create next-generation chemical synthesis” the synergy between synthesizing new bio organisms through synthetic biology and synthesizing novel chemicals gives much hope for development of new approaches to creating complex molecules. Consequently, the emerging discipline of synthetic biology, or the use of engineering principles to design and assemble new biological parts, devices and systems, has allowed for the creation of new biological components whose functions are not found in nature. This in eer branch of science comprises biology, engineering & computer science to develop genetic circuits, enzymes, and any other components to generate a variety of chemical reactions. Chemical synthesis, the formation of new chemical structures from simpler components or precursors, is an essential component of numerous manufacturing operations, and it is a critical component of a wide variety of applications, such as the delivery of innovative therapy, new materials, as well as biological instruments. Some examples of external pressure can include the proactive search for new syntheses and optimization of the reaction pathways, new catalytic systems and methods. Synthetic biology combined with chemistry provides a new way to synthesize different chemicals and create compounds with particular characteristics.

In this review paper, the recent progress and development exhibited in the field of synthetic biology when combined with chemical synthesis will be discussed along with the future prospects and problems of implementing these concepts to develop realistic and effective next-generation chemical synthesis of life. In this chapter, we will discuss how synthetic biology can be used to build biological structures and processes for creating elaborate molecules and look at how these technologies can impact medicine, material science, and chemical biology. Also, we will consider what problems and pioneering possibilities demand the development of new predicates for synthetic biology and chemical synthesis: the lack of effective computational approaches to design and control complex biological systems. Through the presentation of recent literature in the areas of synthetic biology and chemical synthesis, this review seeks to inform future research in constructing cultured complexity of molecules.

Fundamentals of synthetic biology

Synthetic biology is a rapidly advancing field that combines principles from biology, engineering, and technology to design and construct novel biological systems or modify existing ones for specific purposes [1-5]. This powerful approach has significant implications for various applications, including chemical synthesis, where it can be harnessed to produce valuable compounds more efficiently and sustainably [1-3]. One of the key fundamentals of synthetic biology is the use of standardized, interchangeable parts called Bio Bricks. These parts, which include promoters, ribosome binding sites, coding sequences, and terminators, can be assembled in different combinations to create genetic circuits that perform desired functions [1,3]. The development of tools like CRISPR has further advanced synthetic biology by enabling precise genome editing and the creation of genetically modified organisms [4]. Another important aspect of synthetic biology is the use of computational tools for designing and modelling biological systems. Bioinformatics tools allow researchers to analyse and manipulate DNA sequences, while computational models help predict the behavior of engineered systems [4,5]. These tools are crucial for optimizing the design of synthetic pathways and minimizing the time and resources required for experimental testing [2,4]. Synthetic biology has been successfully applied to the production of various chemicals, including biofuels, pharmaceuticals, and specialty chemicals [2-4]. By engineering microorganisms like bacteria and yeast to produce desired compounds, researchers can create more efficient and sustainable production processes compared to traditional chemical synthesis [2,3]. For example, the production of artemisinin, an antimalarial drug, has been significantly improved through the use of synthetic biology techniques [2]. In addition to chemical synthesis, synthetic biology has also been applied to other areas, such as environmental remediation, eco-friendly architecture, and sustainable energy production [3,5]. The development of engineered living materials [ELMs] that possess unique properties like self-organization, self-repair, ansd adaptability has opened up new possibilities in these fields [3]. Despite the significant progress made in synthetic biology, there are still challenges that need to be addressed. Developing reliable and robust methods for engineering biological systems remains a challenge, and further advancements in synthetic biology are needed to fully realize its potential [4]. Additionally, ethical considerations and regulatory frameworks need to be carefully considered as the field continues to evolve [1,5]. In conclusion, synthetic biology is a powerful tool that has the potential to revolutionize chemical synthesis and other areas of science and technology. By harnessing the power of life, researchers can create more efficient and sustainable production processes, leading to the development of novel products and solutions to pressing global challenges.

Principles of synthetic biology

Synthetic biology is an emerging field that applies engineering principles to biological systems to create novel biological functions and devices. The core principles of synthetic biology are centred around the design, construction, and testing of biological systems to achieve specific goals, such as the production of biofuels, chemicals, and pharmaceuticals [6-8]. These principles are crucial for harnessing the power of life to achieve next-generation chemical synthesis. One of the fundamental principles of synthetic biology is hierarchical design. This involves breaking down complex biological systems into smaller, modular components that can be easily engineered and assembled. This approach allows for the creation of biological devices with well-specified input-output behaviours, which can be used to perform specific functions [6,8]. Another key principle is the use of modular, reusable biological parts. These parts, such as promoters and ribosome binding sites, can be easily combined to form the basis for biological devices. This modularity enables the rapid construction and testing of new biological systems, facilitating the iterative design and optimization process [6,8]. Standard interfaces are essential for the integration of different biological parts and systems. These interfaces ensure that the various components can communicate effectively, allowing for the seamless assembly of complex biological devices [6,8]. Quantitative biology plays a critical role in synthetic biology by providing the necessary tools and methods for understanding and optimizing biological systems. Techniques such as RNA sequencing and mass spectrometer analysis enable researchers to study metabolic processes and identify areas for improvement. This knowledge can then be used to engineer biological systems that are more efficient and effective [7].

The field of synthetic biology is evolving from a single-cell approach to a distributed, population-based approach. This shift is enabling the development of more complex biological systems that can perform tasks such as computation and diagnosis. Population-based microbial computing has the potential to revolutionize the field by allowing for the creation of biological systems that can adapt and respond to changing conditions [8].

As synthetic biology continues to advance, it is essential to consider the potential risks and benefits associated with this technology. The precautionary principle, which emphasizes the need to minimize risks to the environment and human health, is a crucial consideration in the development and application of synthetic biology [9]. In conclusion, the principles of synthetic biology, including hierarchical design, modular, reusable parts, standard interfaces, quantitative biology, population-based microbial computing, and the precautionary principle, are essential for harnessing the power of life to achieve next-generation chemical synthesis. By applying these principles, researchers can design and construct biological systems that are more efficient, effective, and sustainable, ultimately leading to significant advancements in the field.

Techniques 

Synthetic biology is a rapidly advancing field that harnesses the power of life to create novel biological systems and products. This review paper will explore the key techniques used in synthetic biology for next-generation chemical synthesis. Genetic engineering and genome editing techniques are crucial for modifying organisms to produce desired chemicals. Techniques like CRISPR-Cas9 allow for precise manipulation of genes, enabling the introduction of new pathways or optimization of existing ones. This allows for the creation of genetically-modified organisms that can efficiently produce commercially-valuable products on a large scale [10].

Metabolic engineering involves the targeted modification of metabolic pathways within organisms to enhance the production of specific chemicals. This can be achieved through techniques such as gene overexpression, knockouts, and pathway optimization. By manipulating key enzymes and regulatory elements, researchers can redirect the flow of metabolites towards the desired product. Synthetic biology enables the design and construction of novel metabolic pathways from scratch. By combining genetic parts from different organisms, such as promoters, coding sequences, and regulatory elements, researchers can create artificial pathways that produce chemicals not naturally found in the host organism. This allows for the synthesis of a wide range of chemicals, including biofuels, pharmaceuticals, and specialty chemicals. The choice of host organism, or chassis, is crucial for successful chemical synthesis. Researchers use techniques like genome reduction to create streamlined bacterial strains with enhanced growth characteristics and productivity [11,12]. These chassis organisms serve as platforms for the introduction of synthetic pathways, allowing for efficient production of the desired chemicals. Microfluidic technologies and cell-free systems are emerging tools in synthetic biology. Microfluidics enables the precise control and manipulation of small volumes of fluids, allowing for the generation of artificial cells with defined parameters [13]. Cell-free systems, on the other hand, use cell extracts to reconstitute biological processes in vitro, enabling rapid prototyping and optimization of synthetic pathways without the need for living cells. Synthetic biology benefits from the integration of automation and high-throughput screening techniques. Robotic platforms can perform repetitive tasks, such as DNA assembly and strain construction, with high accuracy and speed [10]. High-throughput screening methods allow for the rapid evaluation of large libraries of genetic variants or chemical compounds, accelerating the discovery and optimization of novel chemicals. In conclusion, synthetic biology offers a powerful toolkit for the next-generation of chemical synthesis. By leveraging genetic engineering, metabolic engineering, synthetic pathway design, chassis organism development, microfluidics, and automation, researchers can create efficient and sustainable production platforms for a wide range of chemicals. As the field continues to advance, we can expect to see even more innovative applications of synthetic biology in the years to come.

Tools and technology 

Cyanobacteria have shown significant potential as industrial biotechnology platforms for producing a wide range of bio-products, including biofuels, alcohols, isoprenoids, and recombinant proteins [15]. Recent advances in cyanobacterial “omics” research, improved genetic engineering tools, and the emerging field of cyanobacterial synthetic biology have underpinned this technology [15]. These approaches have enabled the development of elaborate metabolic engineering programs aimed at creating designer strains tailored for different industrial biotechnology applications [15].

Standardization of experimental methods and DNA parts is becoming increasingly necessary as the purpose of synthetic biology is to redesign organisms using engineering principles [16]. The synthetic biology community focusing on the engineering of Saccharomyces cerevisiae has been at the forefront in this area, developing several well-characterized synthetic biology toolkits widely adopted by the community [16]. These toolkits have greatly contributed to the rapid development of many metabolic engineering and diagnostics applications [16].

Tremendous progress has been made in understanding the gut microbiome’s role in human health [14]. Biomaterial technologies have been developed to facilitate the study, analysis, and manipulation of the gut microbiome, including intestinal organoids, gut-on-chip models, and hydrogels for spatial mapping of gut microbiome compositions, microbiome biosensors, and oral bacteria delivery systems [14]. These technologies have played critical roles in investigating and regulating the microbiome-gut-brain axis [14]. In addition to S. cerevisiae, toolkits have been designed for emerging nonconventional yeast species, such as Yarrowia lipolytica, Komagataella phaffii, and Kluyveromyces marxianus [16]. These toolkits have contributed to the rapid development of many metabolic engineering and diagnostics applications [16]. However, the yeast community still has a long journey to go to exploit synthetic biology in more sophisticated and delicate applications like bio automation [16].

While significant progress has been made in developing tools and technologies for synthetic biology, there are still challenges that need to be addressed to make cyanobacterial industrial biotechnology more feasible in the near future [15]. These challenges include improving the efficiency of genetic engineering tools, enhancing the production of target compounds, and addressing regulatory issues [15]. In conclusion, synthetic biology has provided a wide range of tools and technologies that have enabled the development of innovative solutions for chemical synthesis. From cyanobacteria as chassis for industrial biotechnology to standardized assembly methods for yeast species, these tools have contributed to the rapid advancement of the field. However, there are still challenges that need to be addressed to fully harness the power of synthetic biology for next-generation chemical synthesis [14-16].

Traditional approaches to chemical synthesis

Chemical synthesis has been a cornerstone of modern chemistry, providing access to a wide range of chemical structures that are crucial for various applications in fields such as medicine, materials science, and biotechnology. Traditional approaches to chemical synthesis have been extensively used to produce a vast array of compounds, from simple molecules to complex biomolecules. This review aims to provide an overview of traditional approaches to chemical synthesis, highlighting their strengths and limitations, and discussing their role in the development of next-generation chemical synthesis. One notable example of traditional chemical synthesis is the Vanderbilt Institute of Chemical Biology's Chemical Synthesis Core, established in 2008. Over the past decade, this core has produced numerous synthetic products, including known and designed compounds, which have significantly contributed to advancements in both basic science discoveries and translational research leading to new therapeutics [17]. The core's focus on chemical synthesis highlights the importance of this approach in generating novel compounds that can be used to understand biological processes and develop new treatments.

Another significant area where traditional chemical synthesis plays a crucial role is in the design and synthesis of artificial small molecules for enzyme engineering. These molecules, such as biological metal cluster mimics, coenzyme analogues, designer cofactors, non-natural nucleotides, and non-natural amino acids, have been successfully used to expand the types of enzymatic reactions and metabolic pathways in cells. By incorporating these artificial small molecules into enzymes, researchers can improve enzyme performance and enhance biotechnological applications [18]. The design, synthesis, and applications of these molecules are critical components of traditional chemical synthesis, demonstrating its versatility and importance in synthetic biology.

Traditional chemical synthesis also plays a significant role in the development of synthetic vaccines against cancer. Synthetic vaccines, which contain antigens conjugated with carrier proteins, can overcome the issues associated with whole-cell or pathogen-based vaccines. The synthesis of these antigens and their conjugation with carrier proteins require traditional chemical synthesis techniques, highlighting the importance of these methods in vaccine development [19]. Furthermore, the addition of suitable adjuvants and a proper delivery system are essential for boosting the immune responses of these vaccines, which also rely on traditional chemical synthesis. Traditional chemical synthesis is also essential for improving chemical production in cyanobacteria, which are photosynthetic microorganisms capable of sequestering atmospheric carbon dioxide. By engineering these microorganisms to produce valuable chemical commodities such as biofuels, plastics, and food additives, researchers can develop sustainable alternatives to traditional petrochemical-based synthesis. The challenges in using cyanobacteria for chemical production, such as slower growth and lower product titters, can be addressed through traditional chemical synthesis techniques, such as rewiring carbon fixation and photosynthesis, and the use of new synthetic biology tools like CRISPR [20].

Finally, traditional chemical synthesis is critical for the valorisation of glycerol into propane diol, a valuable biochemical with industrial applications. This process involves both thermochemical and synthetic biology approaches, including hydrogen lysis reactions and fermentative pathways. The synthesis of propane diol from glycerol requires a detailed understanding of the reaction mechanisms involved, which is a key aspect of traditional chemical synthesis [21]. Traditional approaches to chemical synthesis have been instrumental in the development of various compounds and biomolecules. From the production of synthetic products at the Vanderbilt Institute of Chemical Biology to the design and synthesis of artificial small molecules for enzyme engineering, synthetic vaccines, and chemical production in cyanobacteria, traditional chemical synthesis has played a crucial role in advancing our understanding of biological processes and developing new treatments and products. As the field of synthetic biology continues to evolve, traditional chemical synthesis will remain a vital component, providing the foundation for the development of next-generation chemical synthesis methods and applications.

Limitations and challenges

Synthetic biology holds great promise for revolutionizing chemical synthesis, but there are still significant limitations and challenges that need to be addressed. Here are some key issues to consider: Biological systems are inherently complex, with many interacting components and layers of regulation. Fully understanding and modelling these systems is an immense challenge. Even simple organisms have thousands of genes and complex metabolic pathways. Predicting how changes to one part of the system will affect the whole is extremely difficult [22,23].

Synthetic biology aims to make biology easier to engineer by creating standardized, interchangeable parts. However, most biological parts are highly context-dependent and do not function predictably when combined. Promoters, ribosome binding sites, and other genetic elements can have dramatically different activities depending on their genomic context. Achieving true modularity remains an elusive goal [22,24]. Current methods for editing genomes, such as CRISPR-Cas9, have limitations. They can be inefficient, with low rates of desired modifications. Off-target effects are also a concern. Inserting large DNA constructs is challenging. Improved genome engineering tools are needed to fully realize the potential of synthetic biology [23,25]. While proof-of-concept demonstrations of synthetic biology are common, scaling up engineered systems to industrially relevant scales is difficult. Maintaining stability and productivity in large bioreactors is a major challenge. Metabolic engineering often results in a fitness burden on the host organism, which can limit scalability [23, 25]. Most synthetic biology relies on a small number of well-studied model organisms like E. coli and yeast. These hosts have limitations – they may not be able to produce certain chemicals or tolerate harsh industrial conditions. Expanding the range of robust, genetically tractable host organisms is an important goal [22,25].

Engineered organisms will inevitably evolve over time, potentially losing desired traits or acquiring new unintended functions. Predicting and controlling these evolutionary trajectories is very difficult. Safeguards are needed to prevent engineered organisms from persisting in the environment [22]. The rapid pace of synthetic biology innovation is outpacing the ability of regulatory agencies to keep up. There are concerns about potential misuse of the technology for bioweapons or bioterrorism. Ethical issues around creating artificial life and the environmental release of engineered organisms also need to be carefully considered [23]. In conclusion, while synthetic biology has immense potential to transform chemical synthesis, significant challenges remain. Overcoming the complexity of biological systems, achieving true modularity, developing better genome engineering tools, scaling up engineered systems, expanding the range of host organisms, predicting evolutionary outcomes, and addressing regulatory and ethical concerns will all be critical to realizing the full promise of this powerful technology. Continued research, innovation, and responsible development will be key to harnessing the power of life for next-generation chemical synthesis.

Integration of Synthetic Biology and Chemical Synthesis

The integration of synthetic biology and chemical synthesis has revolutionized the field of biotechnology, enabling the design and construction of novel biological systems that can perform chemical reactions with unprecedented precision and efficiency. This synergy has led to significant advancements in the production of chemicals, fuels, and pharmaceuticals, with far-reaching implications for various industries.

One of the key aspects of this integration is the ability to rationally design and synthesize DNA sequences using chemical synthesis techniques. This allows scientists to create novel biological pathways and systems that can be engineered to produce specific chemicals or compounds. For instance, metabolic engineering and synthetic biology have been used to develop microbial hosts that can produce bulk chemicals and fuels, such as biofuels, with improved yields and efficiency [26]. This is achieved by designing and constructing novel metabolic pathways that can be controlled and regulated using synthetic biology tools.

Another critical component of this integration is the development of novel RNA-based mechanisms, such as riboregulators, which provide additional control over gene expression. These mechanisms enable researchers to fine-tune gene expression levels and optimize the production of specific chemicals or compounds [26]. Additionally, advances in computational tools and methods for high-throughput system assembly and analysis have enabled the rapid design and construction of novel biological systems, further accelerating the development of synthetic biology-based chemical synthesis [26]. The integration of synthetic biology and chemical synthesis has also led to significant breakthroughs in the production of pharmaceuticals. For example, synthetic biology has been used to develop novel biosynthetic pathways for the production of complex molecules, such as antibiotics and antimalarial agents, with improved yields and efficiency [26]. This has the potential to revolutionize the production of these critical medicines, making them more accessible and affordable for patients worldwide. Furthermore, the integration of synthetic biology and chemical synthesis has also enabled the development of novel biocatalysts and enzymes that can be used for the production of specific chemicals or compounds. For instance, directed evolution and combinatorial approaches have been used to engineer novel enzymes with improved substrate specificity and catalytic efficiency, enabling the production of complex molecules with unprecedented precision and efficiency [26]. In conclusion, the integration of synthetic biology and chemical synthesis has opened up new avenues for the production of chemicals, fuels, and pharmaceuticals. By leveraging the power of biological systems and the precision of chemical synthesis, researchers can design and construct novel biological systems that can perform chemical reactions with unprecedented precision and efficiency. This synergy has the potential to revolutionize various industries, from biotechnology to pharmaceuticals, and has significant implications for the development of novel medicines and treatments.

Advantages and opportunities

Synthetic biology and chemical synthesis are powerful tools that, when integrated, offer numerous advantages and opportunities for next-generation chemical production. By harnessing the capabilities of biological systems and combining them with the precision of chemical synthesis, researchers can develop efficient and sustainable processes for the manufacture of a wide range of products, from pharmaceuticals to fuels and specialty chemicals [26-28].

One of the key advantages of integrating synthetic biology and chemical synthesis is the ability to produce complex molecules that are difficult or impossible to synthesize using traditional chemical methods alone [27,29]. Enzymes, the catalysts of biological systems, can perform highly specific and efficient reactions under mild conditions, such as ambient temperatures and pressures, in aqueous media, and at neutral pH [27]. This enables the assembly of multistep synthetic pathways for the in vivo production of complex molecules from simple and abundant starting materials [27,28]. In contrast, traditional chemical synthesis often requires harsh conditions, toxic reagents, and multiple purification steps, leading to increased costs and environmental impact [27]. Another advantage of this integration is the potential for more sustainable and environmentally friendly chemical production [26-28]. Biosynthetic approaches can utilize renewable feedstocks, such as plant biomass or CO2, as starting materials, reducing the reliance on fossil fuels [26,28]. Additionally, the use of enzymes and microbial hosts can minimize waste and energy consumption compared to traditional chemical processes [27,28]. Synthetic biology also offers opportunities for the rapid development and optimization of new biosynthetic pathways [26,28,29]. By leveraging tools such as directed evolution, enzyme engineering, and computational design, researchers can create novel enzymes with improved catalytic activity, substrate specificity, and stability [26,29]. These advancements, combined with the ability to assemble and test multiple pathway variants in parallel, can accelerate the discovery and optimization of efficient biosynthetic routes to target molecules [26,28,29]. Furthermore, the integration of synthetic biology and chemical synthesis enables the production of molecules that are not readily accessible through either approach alone [27,29]. By combining the strengths of both disciplines, researchers can develop hybrid strategies that incorporate both enzymatic and chemical steps, allowing for the synthesis of molecules with unique structural features or properties [27,29]. In conclusion, the integration of synthetic biology and chemical synthesis holds great promise for the development of next-generation chemical production processes. By harnessing the power of biological systems and combining it with the precision of chemical synthesis, researchers can create more efficient, sustainable, and versatile approaches to the manufacture of a wide range of products. As the fields of synthetic biology and chemical synthesis continue to advance, the opportunities for collaboration and innovation will only grow, paving the way for a more sustainable and innovative future in chemical production.

Applications in chemical synthesis

One of the key areas where synthetic biology has made significant strides is in the synthesis of chemical structures alternative to those present in nature. Chemical synthetic biology [CSB] is a branch of synthetic biology that focuses on the synthesis of these alternative structures. CSB uses biological parts, synthetic or not, to create new and alternative structures. This approach has led to the development of novel biocatalysts and biosensors, which can be used to produce chemicals in a more efficient and sustainable manner [24].

Another area where synthetic biology has made significant contributions is in the synthesis of functional proteins inside liposomes. Liposomes are semi-synthetic compartments that contain the minimal and sufficient number of components to perform the basic functions of a biological cell. The synthesis of proteins inside these liposomes has opened up new avenues for the production of chemicals and pharmaceuticals. For instance, the assembly of MreB filaments on liposome membranes has been shown to be a promising approach for the synthesis of chemicals [24]. Synthetic biology has also been used to engineer biological systems to produce chemicals. This involves the design and construction of genetic circuits that can be used to regulate the production of specific chemicals. For example, the use of synthetic genetic circuits has been shown to be effective in the production of biofuels and bio products [26,30]. In addition to these applications, synthetic biology has also been used to develop new methods for the synthesis of DNA oligonucleotides. These oligonucleotides are the building blocks of DNA and are used in a wide range of applications, including gene synthesis and gene editing. The development of automated methods for the synthesis of DNA oligonucleotides has significantly reduced the cost and increased the efficiency of these processes [30]. Furthermore, synthetic biology has been used to develop new methods for the assembly of DNA constructs. This involves the use of microarray/microfluidic oligonucleotide synthesis techniques and automated gene synthesis protocols. These methods have made it possible to synthesize large DNA constructs in a relatively short period of time and at a lower cost [30]. In conclusion, synthetic biology has emerged as a powerful tool in the pursuit of next-generation chemical synthesis. The applications of synthetic biology in chemical synthesis have led to significant advancements in the production of chemicals, fuels, and pharmaceuticals. The development of novel biocatalysts, biosensors, and genetic circuits has opened up new avenues for the production of chemicals and pharmaceuticals. Additionally, the development of automated methods for the synthesis and assembly of DNA constructs has significantly reduced the cost and increased the efficiency of these processes.

Engineering Microorganisms for Chemical Production

Microorganisms, such as bacteria, yeast, and fungi, have been engineered to produce a wide range of chemicals, from commodity chemicals like fuels and plant-based nylon to specialty chemicals like fragrances and food additives. This is achieved by introducing specific genes or genetic circuits into the microorganisms, which enable them to produce the desired chemicals. For instance, the yeast *Pichia pastoris* has been engineered to produce a variety of chemicals, including biofuels, bioplastics, and pharmaceuticals [23]. Recent advancements in synthetic biology have enabled the development of novel methods for engineering microorganisms. For example, the use of CRISPR/Cas9 genome editing technology has accelerated the discovery and engineering of metabolite biosynthesis pathways. This technology allows for precise and efficient editing of genes, enabling the rapid development of new biological systems [31]. Another significant development is the integration of synthetic biology with other disciplines, such as materials science and electrical engineering. This has led to the creation of novel bio circuits and biosensors that can be used for chemical production and detection. For instance, researchers have developed a tripartite microbial co-culture system for the de novo biosynthesis of diverse plant phenylpropanoids, which has potential applications in the production of biofuels and pharmaceuticals [32]. Despite the significant progress made in engineering microorganisms for chemical production, there are still several challenges that need to be addressed. One major challenge is the need for more efficient and cost-effective methods for scaling up production. Additionally, there is a need for more robust and stable biological systems that can operate under variable conditions.

To address these challenges, researchers are exploring new methods and technologies. For instance, the use of immobilization and encapsulation techniques has been shown to improve the stability and efficiency of biological systems. Additionally, the integration of synthetic biology with advanced manufacturing technologies, such as 3D printing and microfluidics, is being explored to improve the scalability and precision of chemical production.

Metabolic engineering

Is a crucial aspect of synthetic biology, focusing on the optimization of cellular processes to produce desired compounds from simple substrates. This field has made significant strides in recent decades, leveraging advances in recombinant DNA technology and systems biology to engineer microorganisms for industrial-scale production of valuable metabolites. The synergy between metabolic engineering and synthetic biology is particularly noteworthy, as synthetic biology provides the tools and information necessary for metabolic engineering to achieve its goals. Metabolic engineering involves the manipulation of metabolic pathways to enhance the production of specific compounds. This is often achieved by introducing genetic modifications that alter the expression of enzymes, transporters, and other regulatory elements involved in the metabolic process. For instance, metabolic engineering has been used to produce a wide range of compounds, including biofuels, pharmaceuticals, and industrial chemicals [33-35]. The integration of synthetic biology and metabolic engineering has led to the development of novel strategies for optimizing metabolic pathways. Synthetic biology provides the components and information about different biological phenomena, which metabolic engineering then applies to engineer microbes for industrial-scale production [33]. This synergy is exemplified by the use of CRISPR/Cas9 nuclease cleavage combined with Gibson assembly for seamless cloning, allowing for the rapid and precise modification of genetic sequences [33]. Metabolic engineering has also been used to enhance the production of specific compounds by strengthening fatty acid synthesis modules in microorganisms. For example, the production of iturin A, a green bio surfactant, has been enhanced by strengthening fatty acid synthesis modules in *Bacillus amyloliquefaciens* through metabolic engineering [35].

Optimization of Biosynthetic Pathways

Optimization of biosynthetic pathways is a crucial aspect of synthetic biology, particularly in the context of next-generation chemical synthesis. This approach involves the design and engineering of biological systems to produce specific chemicals or compounds more efficiently and sustainably. Recent research has focused on leveraging advanced computational tools and machine learning algorithms to optimize these pathways, as highlighted by Shields et al. in their 2021 study on Bayesian reaction optimization [36]. This approach has shown significant potential in improving the efficiency and yield of chemical synthesis processes. Another key area of research has been the integration of artificial intelligence and machine learning into the design and optimization of biosynthetic pathways. For instance, the use of neural networks has been explored to predict the optimal conditions for chemical synthesis, as demonstrated by Nor et al. in their 2017 study on medium optimization for lysine-methionine biosynthesis [36]. This integration of AI and synthetic biology has the potential to revolutionize the field by enabling the rapid design and optimization of novel biosynthetic pathways. Furthermore, the development of novel biotechnological tools and techniques has also played a significant role in optimizing biosynthetic pathways. For example, the use of gene editing tools like CRISPR has enabled the precise modification of genes involved in biosynthetic pathways, allowing for more targeted and efficient optimization. This has been demonstrated in studies such as that by Lentin, which used fluorescent proteins to monitor and optimize in vitro genetic organization for cell-free synthetic biology [24]. These advances in biotechnology and computational tools have collectively contributed to significant progress in optimizing biosynthetic pathways for next-generation chemical synthesis.

Biocatalysts: Expanding the Toolbox for Chemical Synthesis

Biocatalysts has emerged as a powerful tool in the field of chemical synthesis, offering a sustainable and environmentally friendly approach to the production of various compounds. This toolbox of enzymes and microorganisms has the potential to revolutionize the way we synthesize chemicals, particularly in the pharmaceutical and chemical industries. In this review, we will delve into the world of biocatalysts, exploring its applications, types of biocatalysts, and the potential for next-generation chemical synthesis. Biocatalysts is the use of enzymes and microorganisms to catalyse chemical reactions. This approach offers several advantages over traditional chemical synthesis methods. Enzymes are highly specific and efficient, allowing for the production of compounds with high levels of activity and selectivity. Additionally, biocatalysts can be conducted under mild conditions, reducing the need for organic solvents and energy input. Biocatalysts can be broadly classified into two categories: enzymes and microorganisms. Enzymes are highly specific proteins that catalyse specific chemical reactions. They are often used in bio catalytic processes due to their high efficiency and selectivity. Microorganisms, on the other hand, are living organisms that can be used to produce compounds through fermentation processes [37].

Biocatalysis has a wide range of applications in the pharmaceutical and chemical industries. Enzymes are used to produce a variety of compounds, including pharmaceuticals, agrochemicals, and food additives. Microorganisms are used in fermentation processes to produce compounds such as biofuels, bioplastics, and bio products [38,39]. Recent advances in biocatalysts have focused on the development of novel enzymes and microorganisms. For example, the use of metagenomics has enabled the discovery of new enzymes with unique bio catalytic properties. Additionally, advances in protein engineering have allowed for the design of enzymes with improved stability and activity. The future of biocatalysis lies in the development of novel enzymes and microorganisms with improved bio catalytic properties. Additionally, advances in biotechnology and genomics will enable the design of more efficient bio catalytic processes. The use of biocatalysts in next-generation chemical synthesis will require the development of novel biocatalysts and bio catalytic processes that can be scaled up for industrial production [40,41]. Biocatalysis is a powerful tool in the field of chemical synthesis, offering a sustainable and environmentally friendly approach to the production of various compounds. The use of enzymes and microorganisms has the potential to revolutionize the way we synthesize chemicals, particularly in the pharmaceutical and chemical industries. As the field continues to evolve, we can expect to see the development of novel biocatalysts and bio catalytic processes that will enable the production of compounds with improved properties and reduced environmental impact.

Enzyme Engineering

Computational tools, such as machine learning and molecular dynamics simulations, have enabled the rational mutagenesis of key catalytic residues for enhanced or altered biocatalysis [42]. These tools have been used to optimize catalysis for native substrates and increase enzyme promiscuity beyond the scope of traditional rational approaches. High-throughput screens, including designer protein-based biosensors with engineered ligand specificity, have also been developed to accelerate the discovery of novel enzymes with desired properties [42]. Directed evolution, a semi-rational approach, has been widely used to engineer genomes and enzyme-coding genes. This method involves the use of novel tools and techniques, such as DNA synthesis, DNA assembly, recombination-mediated genetic engineering, and high-throughput screening, to generate variants with desired properties [43]. Microenvironment engineering strategies have also been employed to optimize enzyme performance by controlling the local environment around the enzyme active site [42]. Enzyme engineering has been applied in various synthetic biology applications, including the production of natural products, such as polyketides and non-ribosomal peptides, and the engineering of metabolic pathways for the production of aromatic polyketides [44,45]. The incorporation of no canonical amino acids via genetic code expansion has also enabled the creation of novel xenobiotic enzymes with tailored properties [46]. Despite the significant progress made in enzyme engineering, several challenges remain. For instance, the rational design of enzyme-coding genes and de novo assembly of a brand-new artificial genome for a desired functionality or phenotype are still difficult to achieve due to our limited understanding of the relationship between sequence and function [43]. Additionally, the development of novel high-throughput screening techniques and computational tools is necessary to accelerate the discovery of novel enzymes with desired properties. In conclusion, enzyme engineering is a vital component of synthetic biology, enabling the design and optimization of biological systems for various applications. The development of novel computational tools, high-throughput screening techniques, and directed evolution strategies has accelerated the discovery of novel enzymes with desired properties. As the field continues to evolve, it is essential to address the remaining challenges and develop new tools and techniques to further advance the field of enzyme engineering in synthetic biology.

Designing Synthetic Pathways for Target Molecules

One approach to designing synthetic pathways involves the use of computational tools to predict and optimize metabolic pathways for the production of target molecules. Tools like Opt Flux [47] and COBRA [48] enable researchers to model and simulate metabolic networks, predict optimal pathways, and identify potential bottlenecks for pathway optimization. By leveraging these computational tools, researchers can streamline the design process, reduce experimental iterations, and improve the efficiency of synthetic pathway construction.

In addition to computational methods, modular assembly of genetic parts has emerged as a powerful strategy for designing synthetic pathways. Modular DNA assembly techniques, such as Golden Gate [49] and Gibson assembly [50], allow researchers to rapidly construct and test different genetic constructs for pathway engineering. This modular approach enables the efficient assembly of genetic elements, such as promoters, coding sequences, and terminators, to create custom-designed pathways for the production of target molecules. Furthermore, directed evolution has been extensively used to engineer enzymes with improved catalytic properties for synthetic pathway design. By subjecting enzymes to iterative rounds of mutagenesis and selection, researchers can evolve enzymes with enhanced substrate specificity, activity, and stability [51]. These evolved enzymes can then be integrated into synthetic pathways to improve the overall efficiency and yield of target molecule production. Research in synthetic biology has made significant strides in designing synthetic pathways for a wide range of target molecules, including pharmaceuticals, biofuels, and specialty chemicals. For example, studies have demonstrated the successful engineering of microbial hosts to produce complex natural products like opioids [52] and terpenoids [53] through synthetic pathways. These achievements highlight the potential of synthetic biology to enable the sustainable production of valuable compounds through bio manufacturing.

Rational design approaches

Rational design approaches in synthetic biology have emerged as a crucial strategy for engineering biological systems with predictable and reliable outcomes. This approach leverages our understanding of biology to build a library of well-characterized, modular biological parts, such as genes and proteins, which can be assembled into new biological systems. The rational design approach is rooted in the idea that, rather than attempting to build biological systems from scratch like computers, we should take advantage of the parts and tools that Nature has given us, with all their wonderful idiosyncrasies. One key aspect of rational design is the use of well-understood biological components. For instance, Pamela Silver and her colleagues have successfully engineered bacteria to remember chemical stimuli by utilizing a well-characterized genetic switch from a virus. This approach demonstrates the potential of rational design in creating biological systems that can perform specific functions. Additionally, the development of modular biological parts, such as genes and proteins, allows for the assembly of new biological systems with predictable outcomes [Silver et al. 2014]. Rational design also involves the use of mathematical modelling and simulation to predict the behavior of biological systems. This is particularly important in synthetic biology, where the complexity and interconnectedness of biological systems make it challenging to design them with the desired properties [54]. By using mathematical models to simulate the behavior of biological systems, researchers can identify potential issues and optimize their designs before actually building the systems [54]. Another important aspect of rational design is the integration of artificial intelligence [AI] and machine learning [ML] techniques. These tools can be used to inform design and automate the analysis of large data sets, which is critical in synthetic biology where the amount of data generated is vast [54]. For example, ML algorithms can be used to identify patterns in data and make predictions about the behavior of biological systems, allowing researchers to optimize their designs more effectively [54]. The rational design approach has been applied in various areas of synthetic biology, including metabolic engineering, minimal genomes, regulatory circuits, and orthogonal Biosystems (Garner 2021). For instance, metabolic engineering involves the design and construction of biological pathways to produce specific chemicals or compounds. Rational design can be used to optimize these pathways by identifying the most effective enzymes and reaction conditions (Garner 2021). In addition to its applications in synthetic biology, the rational design approach has also been used in the development of new biological tools and research methods. For example, the development of CRISPR-Cas9 gene editing technology has been facilitated by rational design, allowing for precise and efficient editing of genes (Garner 2021). In conclusion, rational design approaches in synthetic biology have the potential to revolutionize the field by enabling the predictable and reliable engineering of biological systems. By leveraging our understanding of biology, integrating AI and ML techniques, and using well-characterized biological components, researchers can create biological systems that can perform specific functions and produce desired outcomes. As the field continues to evolve, the rational design approach will play a crucial role in driving innovation and advancing our understanding of biological systems [55,56].

Computer-Aided Design Tools

Computer-aided design [CAD] tools have revolutionized the field of synthetic biology by enabling researchers to design and optimize biological systems with unprecedented precision. This paradigm shift has been facilitated by the integration of computational power and biological knowledge, allowing scientists to harness the power of life for next-generation chemical synthesis. The development of CAD tools in synthetic biology has been driven by the need to overcome the limitations of traditional genetic engineering methods. These methods often relied on trial and error, which could lead to unpredictable outcomes and lengthy development times. In contrast, CAD tools enable researchers to model and simulate biological systems before actual implementation, significantly reducing the risk of errors and improving the efficiency of the design process [57,24]. One of the key CAD tools in synthetic biology is the use of design software. This software allows researchers to design and optimize biological pathways, circuits, and systems using a variety of algorithms and modelling techniques. For example, the iGEM (International Genetically Engineered Machine) competition has developed a range of design tools, including the popular "Lego" Life-Forms to Order approach, which enables researchers to construct biological systems from standardized components. Another important CAD tool is the use of standardized components. This approach involves the development of modular biological parts that can be easily assembled into larger systems. This modularity enables researchers to design and optimize biological systems at multiple scales, from individual genes to entire genomes [57,24]. The integration of CAD tools with advanced manufacturing technologies has further accelerated the development of synthetic biology. For instance, the use of robotic biological fabs and "cloud labs" has enabled the rapid synthesis and assembly of biological systems on an industrial scale (Hessel 2014). This has opened up new possibilities for the production of complex biological systems and the rapid prototyping of new biological designs. The potential applications of CAD tools in synthetic biology are vast and varied. For example, they could be used to design and optimize biological systems for the production of biofuels, pharmaceuticals, and other valuable chemicals. They could also be used to develop new biological sensors and diagnostic tools, as well as to engineer biological systems for environmental remediation and bioremediation [57-59].

Case Studies in Synthetic Biology-Enabled Chemical Synthesis

One of the most notable examples is the microbial synthesis of artemisinic acid, a precursor to the antimalarial drug artemisinin [31]. Researchers engineered yeast to produce artemisinic acid, which is typically extracted from the sweet wormwood plant. This breakthrough not only provides a more reliable and scalable source of the drug but also reduces the reliance on plant cultivation [31].

Another successful case study is the production of 1, 4-butanediol [BDO], a chemical used in the manufacture of plastics, solvents, and textiles. Genomatica, a synthetic biology company, developed a process to produce BDO from renewable feedstocks using engineered E. coli [60]. This process is more environmentally friendly and cost-effective compared to traditional petrochemical-based methods. Synthetic biology has also enabled the production of novel chemicals that are difficult or impossible to synthesize using traditional methods. For example, researchers have engineered bacteria to produce non-natural amino acids, which can be used to create new classes of pharmaceuticals and materials [24,59]. These non-natural amino acids have unique properties that cannot be achieved with the 20 standard amino acids found in nature.

Another exciting application of synthetic biology in chemical synthesis is the production of biofuels. By engineering microbes to efficiently convert biomass into fuels like ethanol or biodiesel, synthetic biology offers a sustainable alternative to fossil fuels [60]. Companies like Amyris have used synthetic biology to develop processes for producing renewable diesel and jet fuel from sugarcane. Synthetic biology has also made significant contributions to the production of fine chemicals and fragrances. Researchers have engineered yeast to produce vanillin, the primary component of vanilla flavour, from ferulic acid [31]. This approach provides a more sustainable and cost-effective alternative to extracting vanillin from vanilla beans. In addition to microbial production, synthetic biology has also enabled the development of cell-free systems for chemical synthesis. These systems use cell extracts or purified enzymes to carry out chemical reactions without the need for living cells [60]. Cell-free systems offer advantages such as faster reaction times, easier purification of products, and the ability to use non-natural substrates. One example of a cell-free system is the production of hydrogen peroxide using an engineered enzyme cascade [60]. Researchers have developed a cell-free system that can produce hydrogen peroxide from glucose, which can be used as a green oxidant in various chemical processes. These case studies demonstrate the immense potential of synthetic biology in revolutionizing chemical synthesis. By harnessing the power of living systems and engineering them to produce desired chemicals, synthetic biology offers a more sustainable, efficient, and versatile approach compared to traditional chemical synthesis methods. As the field continues to advance, we can expect to see even more exciting applications of synthetic biology in the production of chemicals that benefit society and the environment.

Examples from the Pharmaceutical Industry

This field has seen significant advancements in recent years, with companies like Biogen, Novartis, and Pfizer actively involved in its development. Synthetic biology has the potential to transform the way we produce chemicals, including pharmaceuticals, by leveraging the power of biological systems to create novel compounds and improve existing ones. One notable example is Biogen's use of synthetic biology to develop new treatments for diseases such as multiple sclerosis and lymphoma. Biogen has employed synthetic biology to engineer cells that can produce therapeutic proteins more efficiently and effectively than traditional methods. For instance, Biogen's haemophilia a treatment, Eloctate, uses synthetic biology to produce a recombinant factor VIII protein that is more stable and effective than traditional treatments [32].

Novartis has also made significant strides in synthetic biology. The company has developed a platform called "Cellular Immunotherapy" that uses synthetic biology to engineer T-cells to target specific cancers. This approach has shown promising results in clinical trials, with patients experiencing significant tumour regression and improved overall survival rates [31].

Pfizer has also been actively involved in synthetic biology, particularly in the area of gene therapy. The company has developed a platform called "Gene Therapy" that uses synthetic biology to engineer genes to treat genetic disorders such as sickle cell anaemia and muscular dystrophy. Pfizer's gene therapy platform has shown significant promise in preclinical studies, with the potential to revolutionize the treatment of genetic diseases [59]. Other pharmaceutical giants like GSK and Roche have also invested heavily in synthetic biology. GSK has developed a platform called "Synthetic Biology for Infectious Diseases" that uses synthetic biology to engineer bacteria to produce novel antibiotics and vaccines. Roche has developed a platform called "Synthetic Biology for Cancer" that uses synthetic biology to engineer T-cells to target specific cancers [61]. The pharmaceutical industry's investment in synthetic biology is driven by the potential to create novel compounds and improve existing ones. Synthetic biology offers the ability to design and construct new biological pathways, circuits, and systems that can produce novel compounds and improve existing ones. This approach has the potential to revolutionize the way we produce chemicals, including pharmaceuticals, by leveraging the power of biological systems to create novel compounds and improve existing ones. Companies like Biogen, Novartis, and Pfizer are actively involved in the development of synthetic biology, with significant advancements in recent years. The potential of synthetic biology to create novel compounds and improve existing ones makes it an exciting area of research with significant implications for the pharmaceutical industry.

Challenges and Future Directions in Synthetic Biology-Enabled Chemical Synthesis

Synthetic biology has emerged as a powerful tool for engineering biological systems to produce a wide range of chemicals, materials, and fuels. By harnessing the inherent capabilities of living organisms, synthetic biology offers the potential to develop more sustainable and environmentally-friendly alternatives to traditional chemical synthesis [62,60,23]. However, the translation of synthetic biology from the laboratory to real-world applications faces several key challenges that must be addressed. One of the primary challenges is improving the robustness and reliability of engineered biological systems. Many synthetic biology applications require the precise control and optimization of complex metabolic pathways, which can be sensitive to environmental conditions and genetic instability [23]. Developing strategies to enhance the genetic stability, stress tolerance, and predictability of engineered microorganisms is crucial for ensuring the consistent and reliable production of target compounds. This may involve techniques such as adaptive laboratory evolution, genome engineering, and the development of more robust chassis organisms. Another significant challenge is scaling up synthetic biology processes from the laboratory to industrial-scale production. Factors such as mass transfer limitations, bioreactor design, and downstream processing can significantly impact the efficiency and economics of large-scale bio manufacturing [23]. Addressing these scale-up challenges will require interdisciplinary collaboration between synthetic biologists, chemical engineers, and process development experts to optimize the entire production pipeline. In addition to technical challenges, there are also regulatory and societal considerations that must be navigated. As synthetic biology-derived products enter the market, there is a need for robust regulatory frameworks to ensure their safety and environmental sustainability [31]. Engaging with policymakers, stakeholders, and the public to address concerns about biosafety, biosecurity, and ethical implications of synthetic biology will be crucial for its widespread adoption. Looking to the future, several key research directions hold promise for advancing synthetic biology-enabled chemical synthesis. These include the development of more sophisticated computational tools for designing and modelling complex biological systems, the exploration of non-canonical genetic codes and alternative biochemistries, and the integration of synthetic biology with other emerging technologies such as artificial intelligence, robotics, and materials science [62, 60, 23]. By addressing these challenges and pursuing these research directions, synthetic biology has the potential to revolutionize the way we produce chemicals, materials, and fuels, paving the way for a more sustainable and bio-based economy.

Regulatory and Ethical Considerations

As this powerful technology continues to advance, it is crucial to establish robust governance frameworks to ensure its responsible development and application [24,60]. One key regulatory challenge is ensuring the safety and efficacy of synthetic biology-derived chemicals. Since these compounds may have novel structures and properties, traditional toxicology testing methods may not be sufficient. Regulators will need to develop new assessment protocols to evaluate potential risks to human health and the environment [24]. Additionally, the rapid pace of innovation in synthetic biology could outpace the ability of regulatory agencies to keep up, necessitating more agile and adaptive approaches [60]. Another critical issue is the potential for misuse of synthetic biology for nefarious purposes, such as the production of illicit drugs or chemical weapons. Robust biosecurity measures, including secure storage and handling protocols, personnel vetting, and real-time monitoring of suspicious activity, will be essential to mitigate these risks [24]. International cooperation and information sharing among regulatory agencies, law enforcement, and the scientific community will be key to staying ahead of potential threats [60]. Ethical considerations in synthetic biology-enabled chemical synthesis include concerns about the commodification of life, the potential for unintended consequences, and the equitable distribution of benefits and risks. There are valid concerns that treating biological systems as mere tools for chemical production could lead to a devaluation of life and a loss of respect for the natural world [24]. Additionally, the complexity of biological systems means that even well-intentioned interventions can have unforeseen consequences, both locally and globally [60]. To address these ethical concerns, it will be important to engage in ongoing dialogue with diverse stakeholders, including scientists, policymakers, industry representatives, and the general public [24,60]. This dialogue should aim to foster a shared understanding of the potential benefits and risks of synthetic biology, and to develop governance frameworks that balance innovation with responsible stewardship [60]. Principles of responsible research and innovation, such as anticipation, reflexivity, inclusion, and responsiveness, should be embedded into the development and application of synthetic biology-enabled chemical synthesis [60]. In conclusion, while synthetic biology holds immense promise for revolutionizing chemical synthesis, it also raises important regulatory and ethical considerations that must be carefully addressed. By establishing robust governance frameworks, engaging in ongoing dialogue with diverse stakeholders, and adhering to principles of responsible research and innovation, we can harness the power of life for the benefit of humanity while mitigating potential risks and unintended consequences [24,60].

Conclusion

The review paper delves into the transformative potential of synthetic biology in revolutionizing chemical synthesis processes. By marrying biology and engineering, synthetic biology offers a novel approach to understanding and manipulating living organisms at the genetic level to engineer biological systems with specific functions. This interdisciplinary field combines principles from biology, engineering, chemistry, and computer science to design and construct new biological parts, devices, and systems for useful purposes. One of the key advantages of synthetic biology is its modularity, which allows for the use of standardized, interchangeable parts to build complex biological systems. By leveraging standard biological parts like BioBricks and designing genetic circuits, researchers can create new functions and control cellular behavior in a predictable manner. The abstraction hierarchy principle further aids in managing the complexity of designing biological systems by breaking them down into different layers of abstraction. The integration of synthetic biology into chemical synthesis processes has led to the efficient and sustainable production of a wide range of compounds. Case studies from the pharmaceutical industry, fine chemicals, and specialty materials demonstrate the profound impact of synthetic biology in enabling the production of valuable chemicals in a more sustainable and efficient manner. By engineering microorganisms for chemical production through metabolic engineering and optimizing biosynthetic pathways, synthetic biology presents a promising approach for addressing global health challenges and enhancing drug accessibility.

Overall, synthetic biology holds immense promise in transforming the way we discover, manufacture, and deliver lifesaving medicines, ushering in a new era of precision medicine and sustainable healthcare. By harnessing the power of life through synthetic biology, we can unlock new opportunities to address global health challenges, enhance drug accessibility, and pave the way for a more sustainable pharmaceutical industry. The optimization of pathways to convert renewable feedstocks into biofuels further highlights the potential of synthetic biology in providing sustainable alternatives to fossil fuels and enhancing energy security.

1. Cao J, Li Z, Yang X, Hu, Wang P, et al. (2023) . World Journal of Microbiology and Biotechnology 39: 129.
2. Mani V, Park S, Kim JA, Lee SI, Lee K, et al. (2021) . Plants 10: 2179.

, ,

3. Wang Q, Hu Z, Li Z, Liu T, Bian G, et al. (2023) . Advanced Materials Deerfield Beach Fla 2305828.
4. Wang X, Zhou N, Wang B (2023) . Expert Opinion on Drug Discovery 18: 1087-1097.

Google Scholar

5. L眉ddecke T, Paas A, Harris RJ, Talmann L, Kirchhoff KN, et al. (2023) . Frontiers in Bioengineering and Biotechnology 11.
6. Habibi S, Hashim C, Rodriguez MS, Mohamad S, Deris, et al. (2020) . International Conference on Intelligent and Advanced Systems.
7. Song Y, Feng C, Zhou D, Ma Z, He L, et al. (2024) .聽 Quantitative Biology 12: 1-14.
8. Amos M (2014) International Journal of General Systems 43: 770-782.
9. Rodr铆guez L贸pez B (2015) . Rev Derecho Genoma Hum 41: 143-66.

,

10. None SR, None SM, None SC, Choudhury L (2023 World Journal of Biology Pharmacy and Health Sciences 14: 316-331.
11. Ma S, Su T, Lu X, Qi Q (2024) . Critical Reviews in Biotechnology 44: 660-673.
12. IS Ng, Keskin BB, Tan SI (2020) . Biotechnology Journal 15: 1900228.

Google Scholar

13. Supramaniam P, Ces O, Salehi-Reyhani A (2019) . Micromachines 10: 299.
14. Yang L, Hung LY, Zhu Y, Ding S, Margolis KG, et al. (2022) . Research.
15. Al-Haj L, Lui Y, Abed R, Gomaa M, Purton S, et al. (2016) . Life 6: 42.
16. Malc谋 K, Watts E, Roberts TM, Auxillos JY, Nowrouzi B, et al. (2022) . ACS Synthetic Biology 11: 2527-2547.
17. Kim K, Christov PP, Romaine 聽I, Tian J, Jana S, et al. (2021) . ACS Chemical Biology 16: 787-793.
18. Liu F, He L, Dong S, Xuan J, Cui Q, et al. (2023) . ProQuest 5850.
19. Hossain F, Kandalai S, Zhou X, Zhang N, Zheng Q, et al. (2022) . Molecules 27: 6933.
20. Treece TR, Gonzales JN, Pressley JR, Shota A (2022) Sec. Synthetic Biology 10.
21. Arash Y, Bot A, Nanda S, Dalai AK (2023) . Fermentation 9: 894-894.
22. Gallup O, Ming H, Ellis T (2021) . Engineering Biology 5: 51-59.
23. Brooks SM, Alper HS (2021) . Nature Communications.
24. Chiarabelli C, Stano P, Luisi PL (2013) . Frontiers in Microbiology 4.
25. Adesina O, Anzai I, Avalos J, Barstow B (2017) . Chem 2: 20-51.
26. Carothers JM, Goler JA, Keasling JD (2009) . Current Opinion in Biotechnology 20: 498-503.
27. Wiltschi B, Gliederv A (2024) .
28. Luo Y, Lee JK, Zhao H (2013) . Chemical Engineering Science 103: 115-119.
29. Liang J, Luo Y, Zhao H (2010) . Wiley Interdisciplinary Reviews: Systems Biology and Medicine 3: 7-20.
30. Hughes RA, Ellington AD (2017) Cold Spring Harbor Perspectives in Biology 9: a023812.
31. Yan X, Liu X, Zhao C, Chen GQ (2023) . Signal Transduction and Targeted Therapy 8: 1-33.
32. Mao N, Aggarwal N, Poh CL, Cho BK, Kondo A, et al. (2021) Advanced Genetics 2: 1.
33. Garc铆a-Granados R, Lerma-Escalera JA, Morones-Ram铆rez JR (2019) . Frontiers in Bioengineering and Biotechnology 7.
34. M. Ahmed (2018) . Springer International Publishing AG.
35. Wang J, Qi Q, Sheng Wu, Gong Cheng, Xue Bao, et al. (2009) . Front. Bioeng. Biotechnol 10.
36. Taylor CJ, Pomberger A, Felton KC, Grainger R, Barecka M, et al. (2023) . Chemical Reviews 123: 3089-3126.

, ,

37. Goswami A, Stewart JD (2016) . Elsevier eBooks 1-38.
38. Ahsan WA, Hussain A, Lin C, Nguyen MK (2023) . Catalysts 13: 294.
39. Ran N, Zhao L, Chen Z, Tao J (2008) . Green Chem 10: 361-372
40. O’Connell A, Barry A, Burke 聽AJ, Hutton AE, Bell EL, et al. (2024) . Chemical Society Reviews 53: 2828-2850.
41. Sousa J, Silv茅rio SC, Costa 脗A, Rodrigues LR (2022) . Catalysts 12: 385-385.
42. Calzini MA, Malico AA, Mitchler MM, Williams GJ (2021) . Protein Engineering, Design and Selection 34: gzab015.
43. Kang Z, Zhang J, Jin P, Yang S (2015) . Bioengineered 6: 136-140.
44. Yang D, Eun H, Pricilia C (2023) . International Journal of Molecular Sciences 24: 8923-8923.
45. Dalby PA (2014) Semantic Scholar 1: 79-105.
46. Giger S, Buller R (2023) . Chimia 77: 395-402.
47. Rocha I, Maia P, Evangelista P, Vila莽a P, Soares S, et al. (2010) . BMC Systems Biology 4.
48. Thiele I, Palsson B脴 (2010) . Nature Protocols 5: 93-121.

, ,

49. Engler C, Gruetzner R, Kandzia R, Marillonnet S (2009) . PLoS ONE 4: e5553.

, ,

50. Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA, et al. ( 2009) . Nature Methods 6: 343-345.

, ,

51. Reetz MT (2019) ? Accounts of Chemical Research 52: 336-344.
52. Galanie S, Thodey K, Trenchard IJ, Filsinger M, Interrante, et al. (2015) . Science 349: 1095-1100.
53. Paddon CJ, PJ Westfall, Pitera DJ, Benjamin K, Fisher K, et al. (2013) . Nature 496: 528-532.

, ,

54. Goshisht MK (2024) Machine learning and deep learning in synthetic biology: Key architectures, applications, and challenges. ACS Omega 9: 9921-9945.
55. Kathryn L, Garner (2021) . Essays in Biochemistry 65: 791-811.

, ,

56. Silver P, Staff S (2003) . Nature Journal 27: 341-353.
57. Young E, Alper H (2010) . Journal of Biomedicine and Biotechnology 1-12.
58. Hessel A (2014) . Science Progress 97: 387-398.
59. Benner SA, Yang Z, Chen F (2011) Comptes Rendus Chimie 14: 372-387.
60. El Karoui M, Hoyos-Flight M, Fletcher L (2019) . 聽Frontiers in Bioengineering and Biotechnology 7.
61. Church GM, Elowitz MB, Smolke CD, Voigt CA, Weiss R, et al. (2014) . Nature Reviews Molecular Cell Biology 15: 289-294.
62. Jewett M, Shao-Horn Y, Voigt C (2018) . Future Directions of Synthetic Biology for Energy and Power.