Natural products are organic secondary metabolites produced by all forms of life. In their native environment, natural products mediate intra- and interspecies communication. Natural products are useful in the clinic – a majority of drugs and pharmaceuticals are derived from natural products. The Agarwal laboratory seeks to understand how gene encoded enzymes construct natural product organic structures starting from simple biologically available starting materials. With the underlying motivation to reconstitute natural product biosynthetic pathways in the laboratory, we use a multidisciplinary approach involving metabolomics, (meta)genomics, enzymological assays, and structural biology to query the intricate enzymological chemistry which underlies natural product biosynthesis, and the metabolomic and genomic complexity of multi-organismal ecological niches in which natural products are produced. This seminar will highlight recent progress in two research directions: total in vitro reconstitution of polyketide synthases to reveal gatekeeping selectivity of ketosynthase domains, and the discovery and synthetic biological elaboration of an exceptionally widely distributed biosynthetic gene loci encoding brominated ribosomally synthesized and post-translationally modified peptide natural products. In both research areas, efforts toward rational engineering of respective natural product biosynthetic pathways will be described, with forays into basic enzymology which enables, or stymies success of these engineering efforts.
Dr. Vinayak (Vinny) Agarwal is a faculty member in the School of Chemistry and Biochemistry and School of Biological Sciences at Georgia Tech. Prior to starting as an Assistant Professor at Georgia Tech in 2017 where he promoted with tenure to Associate Professor in 2023, he obtained his PhD at the University of Illinois Urbana-Champaign followed by postdoctoral work at the Scripps Institution of Oceanography in San Diego. His lab uses multiple techniques spanning genomics, biochemistry, and structural biology to discover and understand how enzymes work as catalysts to construct complex bioactive organic molecules in nature. Vinny has been recognized by the K99/R00 Pathway to Independence Award and the Maximizing Investigators' Research Award by the NIH, the NSF CAREER award, the Alfred P. Sloan Foundation Fellowship, the National Academy Kavli Fellowship, the Cottrell Scholar Award, and the Camille Dreyfus Teacher-Scholar Award. Vinny is firmly committed to diversity, inclusion, and equity in the laboratory and the classroom.Â