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Bio Summit & Molecular Biology 2016
October 10-12, 2016
Volume 6, Issue 6(Suppl) J Biotechnol Biomater
ISSN: 2155-952X JBTBM, an open access journal
conferenceseries .com
October 10-12, 2016 Dubai, UAE
2nd World Congress on
Bio Summit & Molecular Biology Expo
Priti Saxena, J Biotechnol Biomater 2016, 6:6(Suppl)
Dissecting functional importance of polyketide modifying enzymes in mycobacterial biology
Priti Saxena
South Asian University, India
C orynebacterineae includes some of the deadliest human pathogens such as, Mycobacterium tuberculosis (Mtb ) and
Mycobacterium leprae. In 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. Long-chain alkylresorcinols and alkylpyrones replace membrane phospholipids in
Azotobacter cells differentiating into dormant cells. Alkyl phloroglucinols are key signaling factors required for differentiation
and development of Dictyostelium molds. These phenolic lipids in Streptomyces confer resistance to β-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. Type III
polyketide quinones have been recently identified to be key molecules required for anaerobic respiration in mycobacterial
biofilms. Interestingly, many of the type III polyketides require modifying enzymes in order to become fully functional. These
modifying enzymes are generally cytochrome P450s, desaturases, methyltransferases, sulfotransferases, oxidoreductases and
others. Often these modifying enzymes are present in cluster with type III pks genes and transcriptionally expressed together.
In this study, we have identified two unique polyketide clusters in Mycobacterium marinum. Our biochemical, mutational
and structural studies provide evidence for an unanticipated potential of these proteins to cyclize 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 metabolites are variously modified to become biologically active. 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 ofGenomics
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.