New Paper in Angew Chem Int by the Piel Lab

Thioesterases(TEs)are fundamentally important enzymes present in all bacteria and eukaryotes, where they have conserved functions in fatty acid biosynthesis and secondary metabolism. This work providesthe first structural insights into a functionally distinct group of TEsthat perform diverse acylations in polyketide and peptide biosynthesis(TEBs). Structural analysis of the oocydin (OocS) TEBdomain facilitated identificationand engineering of the active site to modulateacyl-group acceptance. In this way, we achieved higher reactivity using a structure-based approach, building a foundation for biocatalytic development of TEB-mediatedO-acylation, a modification known to improve the bioactivity of oocydin-type polyketides. Lastly, the promiscuity of the OocS TEBmotivated us to investigate, and ultimately provide evidence for, the production of longer chain branched oocydins in the native host Serratia plymuthica4Rx13.This work frames the OocS TEBand homologs as invaluable synthetic biology tools for polyketide drug development.