The Final Steps of Bacillaene Biosynthesis in Bacillus amyloliquefaciens FZB42: Direct Evidence for β,γ Dehydration by a trans-Acyltransferase Polyketide Synthase
The Final Steps of Bacillaene Biosynthesis in Bacillus amyloliquefaciens FZB42: Direct Evidence for β,γ Dehydration by a trans-Acyltransferase Polyketide Synthase
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DOI：
10.1002/anie.200905468
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发表时间：
2010-01-01
影响因子：
16.6
通讯作者：
Piel, Joern
中科院分区：
文献类型：
--
作者：
Moldenhauer, Jana;Goetz, Daniel C. G.;Piel, Joern
The antibiotic bacillaene [1](1; Scheme 1) is the prototype of a growing class of polyketides synthesized by a family of polyketide synthases (PKSs) termed trans-acyltransferase (AT) PKSs.[2, 3] These poorly studied enzymes are giant multimodular proteins that have evolved independently [4] from the textbook (cis-AT) PKSs involved in, for example, erythromycin biosynthesis.[5] Since they are rare in actinomycetes, the first model organisms used for studies on polyketide biosynthesis, trans-AT PKSs have long been overlooked. However, they are now known to be widespread among many other rich natural product sources and responsible for the production of several pharmacologically relevant polyketides, including antibiotics of the mupirocin [2c] and streptogramin [2g] groups and the antitumor drug candidate bryostatin 1.[6b] trans-AT PKSs have also attracted considerable ecological interest, since they occur in bacteria with unusual lifestyles, such as symbionts, pathogens, and anaerobes.[2, 3, 6] Another peculiarity that sets them apart from cis-AT enzymes and raises fundamental questions about how polyketides are assembled by these proteins is the high frequency of biosynthetic features that do not conform with classical PKS rules.[2, 3, 7]During functional studies with 1 as a model, we discovered that deletion of the thioesterase (TE) domain, which releases the assembled polyketide chain from the PKS,[8] results in the production of virtually all intermediates.[9] This unusual phenomenon enabled us to unravel a large part of bacillaene biosynthesis and, in combination with phylogenetic analyses, to establish a set of colinearity rules that can be applied to the prediction and discovery of natural products from trans-AT PKS sequences.[3]
