5cxo

Publication Abstract from PubMed

Tetrahydropyran rings are a common feature of complex polyketide natural products, but much remains to be learned about the enzymology of their formation. The enzyme SalBIII from the salinomycin biosynthetic pathway resembles other polyether epoxide hydrolases/cyclases of the MonB family, but SalBIII plays no role in the conventional cascade of ring opening/closing. Mutation in the salBIII gene gave a metabolite in which ring A is not formed. Using this metabolite in vitro as a substrate analogue, SalBIII has been shown to form pyran ring A. We have determined the X-ray crystal structure of SalBIII, and structure-guided mutagenesis of putative active-site residues has identified Asp38 and Asp104 as an essential catalytic dyad. The demonstrated pyran synthase activity of SalBIII further extends the impressive catalytic versatility of alpha+beta barrel fold proteins.

Enzymology of Pyran Ring A Formation in Salinomycin Biosynthesis.,Luhavaya H, Dias MV, Williams SR, Hong H, de Oliveira LG, Leadlay PF Angew Chem Int Ed Engl. 2015 Sep 17. doi: 10.1002/anie.201507090. PMID:26377145^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.