Assistant Professor of Chemistry, Physics graduate Program member
Structural insights into the biosynthesis and bioactivity of natural products
Natural products provide a powerful foundation from which to develop novel therapeutics. Despite their utility, our understanding of both their biosynthesis and mechanisms of action are often incomplete, due in part to the scarcity of structural data depicting their interactions with associated bio-synthetic enzymes and/or targets.
Ribosomally synthesized and post-translationally modified peptides (RiPPs), for example, are a diverse class of bioactive peptides whose simple biosynthetic pathways make them attractive for bio-engineering efforts. However, the structural basis for substrate recognition and recruitment by their respective tailoring enzymes remains unclear. Hydroxyalkylquinolines (HAQs), by contrast, have been studied extensively for their marked antimicrobial activity, yet insights into the origin of this activity are limited.
In this talk, I will present X-ray crystallographic data and computational modeling studies that elucidate the structure and dynamics of associated enzyme-ligand interactions. In particu-
lar, our results provide new insights into the role of a putative substrate-
binding domain associated with RiPP-biosynthesis via study of the radical S-adenosylmethionine (SAM) enzyme, SuiB, and confirm the hypothesis that competition with the co-substrate ubiquinone is the basis for dihydroorotate dehydrogenase inhibition by bacterial HAQs.
THURSDAY I NOV. 10 I 3:30-4:30 PM CST I HYBRID SEMINAR