Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/235488
Type: Artigo de periódico
Title: Macrodiolide Formation By The Thioesterase Of A Modular Polyketide Synthase.
Author: Zhou, Yongjun
Prediger, Patrícia
Dias, Luiz Carlos
Murphy, Annabel C
Leadlay, Peter F
Abstract: Elaiophylin is an unusual C2-symmetric antibiotic macrodiolide produced on a bacterial modular polyketide synthase assembly line. To probe the mechanism and selectivity of diolide formation, we sought to reconstitute ring formation in vitro by using a non-natural substrate. Incubation of recombinant elaiophylin thioesterase/cyclase with a synthetic pentaketide analogue of the presumed monomeric polyketide precursor of elaiophylin, specifically its N-acetylcysteamine thioester, produced a novel 16-membered C2-symmetric macrodiolide. A linear dimeric thioester is an intermediate in ring formation, which indicates iterative use of the thioesterase active site in ligation and subsequent cyclization. Furthermore, the elaiophylin thioesterase acts on a mixture of pentaketide and tetraketide thioesters to give both the symmetric decaketide diolide and the novel asymmetric hybrid nonaketide diolide. Such thioesterases have potential as tools for the in vitro construction of novel diolides.
Subject: Biosynthese
Diolide
Elaiophylin
Polyketid-synthase
Thioesterase
Rights: embargo
Identifier DOI: 10.1002/ange.201500401
Address: http://www.ncbi.nlm.nih.gov/pubmed/?term=26300568
Date Issue: 2015
Appears in Collections:Unicamp - Artigos e Outros Documentos

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