Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Enzymology of Pyran RingA Formation in Salinomycin Biosynthesis

Full text
Author(s):
Luhavaya, Hanna [1] ; Dias, Marcio V. B. [2] ; Williams, Simon R. [3] ; Hong, Hui [1] ; de Oliveira, Luciana G. [4] ; Leadlay, Peter F. [1]
Total Authors: 6
Affiliation:
[1] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA - England
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508000 Sao Paulo, SP - Brazil
[3] Univ Cambridge, Univ Chem Lab, Cambridge CB2 1EW - England
[4] Univ Campinas UNICAMP, Dept Organ Chem, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION; v. 54, n. 46, p. 13622-13625, NOV 9 2015.
Web of Science Citations: 18
Abstract

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 ringA is not formed. Using this metabolite invitro as a substrate analogue, SalBIII has been shown to form pyran ringA. 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 + barrel fold proteins. (AU)

FAPESP's process: 10/15971-3 - Structural characterization of enzymes from antibiotic biosynthetic pathways with biotechnological interest
Grantee:Marcio Vinicius Bertacine Dias
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 11/17510-6 - Studies towards biosynthesis and combinatorial biosynthesis of ionophoric polyether salinomycin
Grantee:Luciana Gonzaga de Oliveira
Support Opportunities: Scholarships abroad - New Frontiers