Opportunities, and Challenges in Engineering Natural Product Biosynthetic Pathways

Apr 10, 2024, 4:00 pm5:00 pm



Event Description

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.