Reprogramming of the Aurantinin Polyketide Assembly Line to Synthesize Auritriacids by Excising an Atypical Enoyl-CoA Hydratase Domain.

Modular polyketide synthases (PKSs) are capable of synthesizing diverse natural products with fascinating bioactivities. Canonical enoyl-CoA hydratases (ECHs) are components of the β-branching cassette that modifies the polyketide chain by adding a β-methyl branch. Herein, it is demonstrated that the deletion of an atypical ECH Q domain (featuring a Q 280 residue) of Art21, a didomain protein contains an ECH Q domain and a thioesterase (TE) domain, reprograms the polyketide assembly line from synthesizing tetracyclic aurantinins (ARTs) to bicyclic auritriacids (ATAs) with much lower antibacterial activities. Genes encoding the ECH Q -TE didomain proteins distribute in many PKS gene clusters from different bacteria. Significantly, the ART PKS machinery can be directed to make ARTs, ATAs, or both of them by employing appropriate ECH Q -TE proteins, implying a great potential for using this reprogramming strategy in polyketide structure diversification.