Structural and functional insights into hybrid AT-less megaenzyme synthase (NRPS) and DNA-MsDps2 complexes using single particle cryo-EM

includes bibliographic reference and index

PhD; 2023; Molecular biophysics unit

Microorganisms, mainly bacteria and fungi, are the producers of structurally diverse, complex organic compounds called as secondary metabolites. These metabolites include polyketides (PKs), non-ribosomal peptides (NRPs), and hybrid PKs/NRPs. The final products from these three classes display different characteristics like antibiotics, antiparasitic agents, antifungals, anticancer drugs, and immunosuppressants. As these products have wide range of potential application in pharmaceuticals, a number of biochemical studies have been carried out to elucidate of their biosynthetic pathways. The biosynthesis of these products is catalysed by large, multi-modular proteins including the NRPSs (non-ribosomal peptide synthases), the PKSs (polyketide synthases) and hybrid NRPS/PKS. Knowledge of the quaternary structure of PKS, NRPS and hybrid NRPS/PKS assembly line enzymes have been topic of interest since it helps not only in elucidating the crosstalk between different domains but also useful in modification of products.