Enzymology of Pyran Ring A Formation in Salinomycin Biosynthesis
Dias, Marcio VB
de, Oliveira Luciana G
A novel pyran synthase in salinomycin biosynthesis
Angewandte Chemie International Edition
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Luhavaya, H., Dias, M. V., Williams, S., Hong, H., de, O. L. G., & Leadlay, P. (2015). Enzymology of Pyran Ring A Formation in Salinomycin Biosynthesis. Angewandte Chemie International Edition, 54 13622-13625. https://doi.org/10.1002/anie.201507090
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 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 α + β barrel fold proteins.
biosynthesis, polyketide synthase, dehydratase, cyclase, polyether
We gratefully acknowledge BBSRC (project grant BB/J007250/1 to P.F.L.) and the University of Cambridge (Overseas Research Studentship to H.L.). S.R.W. acknowledges the support of a studentship from the Todd-Raphael Fund and Prof. Ian Paterson. M.B.V.D. (grant 2010/15971-3) and L.G. de O. (grant 2011/17510-6) acknowledge the support of the São Paolo Research Foundation (FAPESP) of Brazil.
External DOI: https://doi.org/10.1002/anie.201507090
This record's URL: https://www.repository.cam.ac.uk/handle/1810/250491