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Abstract

Corynebacterineae includes some of the deadliest human pathogens such as, Mycobacterium tuberculosis (Mtb) and Mycobacterium leprae. Recent years have seen a remarkable increase in our understanding of secondary metabolic networks that impart these potentials to this order of organisms. One of the major secondary metabolites is polyketides. Comparative genomics of closely related genera from this family have revealed unusual polyketide biosynthetic potentials with the existence of genes homologous to type III pkss. Type III polyketide products in recent years have been remarkably associated with cell wall modifications. Longchain alkylresorcinols and alkylpyrones replace membrane phospholipids in Azotobacter cells differentiating into dormant cells. Alkylphloroglucinols are key signaling factors required for differentiation and development of Dictyostelium molds. These phenolic lipids in Streptomyces confer resistance to �²-lactam antibiotics by altering properties of the cytoplasmic membrane. Although, resorcinolic/phloroglucinolic lipids are not known in Mtb, our functional characterization of PKS18 identified alkylpyrones as major polyketide products in vitro. These metabolites are crucial components of pollen exine in Arabidopsis thaliana and could be synthesized by PKSIIINc from Neurospora crassa. Our biochemical, mutational and structural studies provide evidence for an unanticipated potential of these proteins to cyclise a common biosynthetic intermediate to generate chemically and structurally distinct metabolic entities utilizing a single catalytic site and a limited pool of precursor molecules. These observations not only provide interesting clues to the possible role of these small molecules in Corynebacterineae physiology and virulence but can be further exploited for generating a reservoir of structurally and chemically distinct unnatural bioactive scaffolds.

Biography

Priti Saxena completed her PhD in Chemical Biology from National Institute of Immunology, New Delhi. She worked as a Scientist Fellow at Institute of Genomics and Integrative Biology, Delhi and has published several articles in reputed high impact journals. She has been awarded with the premier fellowship of Innovative Young Biotechnologist Award (IYBA) of DBT, India and SAU Intramural Grant of South Asian University, India. Her research interests focus on delineating molecular mechanisms underlying mycobacterial pathogenesis in the capacity of an Assistant Professor at South Asian University, India.

Email: psaxena@sau.ac.in