Artículos de revistas
Macrodiolide Formation By The Thioesterase Of A Modular Polyketide Synthase.
Registration in:
Angewandte Chemie (weinheim An Der Bergstrasse, Germany). v. 127, n. 17, p. 5321-5324, 2015-Apr.
0044-8249
10.1002/ange.201500401
26300568
Author
Zhou, Yongjun
Prediger, Patrícia
Dias, Luiz Carlos
Murphy, Annabel C
Leadlay, Peter F
Institutions
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. 127 5321-5324