Structural and Functional Trends in Dehydrating Bimodules from trans-Acyltransferase Polyketide Synthases.

ABSTRACT: In an effort to uncover the structural motifs and biosynthetic logic of the relatively uncharacterized trans-acyltransferase polyketide synthases, we have begun the dissection of the enigmatic dehydrating bimodules common in these enzymatic assembly lines. We report the 1.98 Å resolution structure of a ketoreductase (KR) from the first half of a type A dehydrating bimodule and the 2.22 Å resolution structure of a dehydratase (DH) from the second half of a type B dehydrating bimodule. The KR, from the third module of the bacillaene synthase, and the DH, from the tenth module of the difficidin synthase, possess features not observed in structurally characterized homologs. The DH architecture provides clues for how it catalyzes a unique double dehydration. Correlations between the chemistries proposed for dehydrating bimodules and bioinformatic analysis indicate that type A dehydrating bimodules generally produce an ?/?-cis alkene moiety, while type B dehydrating bimodules generally produce an ?/?-trans, ?/?-cis diene moiety.

SUBMITTER: Wagner DT 

PROVIDER: S-EPMC5553570 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature