Chemical Biology Group (CBG) at FLSB, SAU is keenly interested in delineating the functional significance of polyketide lipids in the biology of Mycobacteria and related pathogenic Corynebacterineae. We attempt to identify biological role of polyketide synthases and polyketide modifying enzymes in pathogenesis of corynebacterineae members and dissect molecular intricacies mediating host-pathogen interplay. A multipronged approach is utilized in the laboratory that focuses on different aspects of the problem. Our interdisciplinary research works at the interface of biology, chemistry, physics and computational sciences and relies on latest tools and techniques in chemical biology including crystallography and mass spectrometry based high-resolution proteomics, metabolomics and lipidomics. Our extensive biochemical, protein engineering and chemical biology approaches have identified novel molecular potentials of key enzyme systems and products that facilitate mycobacterial survival in stationary biofilm pathogenic states.

To dissect host-pathogen interactions we use Zebrafish as an in vivo system. Infection studies with CRISPR knockout and complemented strains of mycobacteria have revealed important immunological parameters during established active mycobacterial pathogenesis. Our research provides evidence for involvement of polyketide biosynthesizing systems in mediating molecular events that dictate pathogenic and persistent states of mycobacteria. These studies should potentially reveal new prospective drug-targets and provide leads for novel intervention strategies.

Polyketides are a family of structurally and chemically related metabolites with immense biological potentials and bioactivities. The unique chemical architecture of these natural products facilitates interactions with various bio-molecules conferring potent bio-functionalities. Our metabolomic studies, aimed to dissect the molecular function of polyketide metabolites and associated modifications have unraveled chemically diverse and structurally distinct class of novel mycobacterial lipids. Biochemical and structural characterization of the polyketide biosynthetic and modifying enzymes have not only revealed their catalytic functioning but also provided clues to exploit these proteins for generating a series of architecturally and chemically distinct scaffolds with diverse bioactive potentials that can be further studied for their unique applications. Several of these molecules display therapeutic properties and are important to the cosmeceutical, nutraceutical and pharmaceutical industry. Using fundamentals of medicinal chemistry and drug discovery in conjunction with synthetic and combinatorial biology methods, we extensively work towards designing microbial hosts for specific production of novel bio-functional metabolites that can be utilized for mass production through bio-manufacturing and translated for product development.