Unique features of the ketosynthase domain in a nonribosomal peptide synthetase-polyketide synthase hybrid enzyme, tenuazonic acid synthetase 1.

ABSTRACT: Many microbial secondary metabolites are produced by multienzyme complexes comprising nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). The ketosynthase (KS) domains of polyketide synthase normally catalyze the decarboxylative Claisen condensation of acyl and malonyl blocks to extend the polyketide chain. However, the terminal KS domain in tenuazonic acid synthetase 1 (TAS1) from the fungus Pyricularia oryzae conducts substrate cyclization. Here, we report on the unique features of the KS domain in TAS1. We observed that this domain is monomeric, not dimeric as is typical for KSs. Analysis of a 1.68-Å resolution crystal structure suggests that the substrate cyclization is triggered via proton abstraction from the active methylene moiety in the substrate by a

SUBMITTER: Yun CS 

PROVIDER: S-EPMC7450107 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature