Beta‐Lactam and Beta‐Lactone Antibiotics from Plant Microbiomes

Abstract

Plant microbiomes are rich sources of metabolites that can drive important plant-microbe and microbe-microbe interactions. The story of two microbial metabolites, tabtoxinine-beta-lactam (TBL) and obafluorin (OBI), will be presented. TBL is produced by plant pathogenic Pseudomonas syringae and OBI is produced by plant symbiotic Pseudomonas fluorescens. Interestingly, both TBL and OBI possess strained four-membered heterocycles, a beta-lactam and beta-lactone, respectively, that are critical for biological activity. TBL is a potent inhibitor of plant and bacterial glutamine synthetase and increases the virulence of producing P. syringae. TBL production by P. syringae also suppresses the growth of competing bacteria including P. fluorescens. In contrast to traditional beta-lactam antibiotics such as penicillin, TBL is a non-covalent inhibitor of glutamine synthetase and the beta-lactam stays intact during enzyme inhibition. The C3-hydroxyl group of TBL is phosphorylated in the glutamine synthetase active site and phospho-TBL stabilizes the enzyme in a closed conformation by mimicking the tetrahedral transition state of the biosynthetic reaction. The biological target of OBI is unknown. OBI shows broad spectrum antibacterial activity against Gram-positive and Gram-negative bacteria, including P. syringae. Plant associated P. fluorescens produce OBI via a nonribosomal peptide synthetase with a novel Cys-active site thioesterase domain that catalyzes beta-lactone ring formation during product release. Biosynthetic, target inhibition, and microbiological studies will be presented to highlight the role that TBL and OBI play in the dynamics of plant-pathogen, plant-symbiont, and pathogen-symbiont interactions within plant microbiomes. Support or Funding Information Support for this work was provided by WUSTL and the Research Corporation for Science Advancement through a Cottrell Scholars Award. Structures ot beta-lactam and beta-lactone antibiotics produced by plant-associated Pseudomonads. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.