Genetic interception and structural characterization of thiopeptide cyclization precursors from Bacillus cereus.

Genetic interception and structural characterization of thiopeptide cyclization precursors from Bacillus cereus.
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DOI:
10.1021/ja104524q
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发表时间:
2010-09-08
影响因子:
15
通讯作者:
Acker, Michael G.
Acker, Michael G.
中科院分区:
化学1区
文献类型:
--
作者:
Bowers, Albert A.;Walsh, Christopher T.;Acker, Michael G.

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硫代西林的吡啶核心一直被假定为是由两个脱氢丙氨酸的后期尾对尾缩合产生的。tclM(一种被提出的“Diels-Alderase”)的遗传破坏允许分离该吡啶环的无环前体。分离的产物具有硫代西林通常显示的完整的翻译后修饰,包括脱氢丁炔、噻唑、C-末端脱羧和两种先前未证实的脱氢丙氨酸。此外,前导肽已经经历了广泛的N-末端降解,剩余的前导肽残基已经被N-琥珀酰化。这些结果鉴定了TclM及其在其他噻唑基肽生产菌株中的同系物作为负责这类分子核心处的跨环杂环化的酶。
The pyridine core of the thiocillins has long been postulated to arise from a late-stage tail-to-tail condensation of two dehydroalanines. Genetic disruption oftclM, a proposed “Diels−Alderase”, allowed isolation of acyclic precursors to this pyridine ring. The isolated products possess the full cohort of post-translational modifications that are normally displayed by the thiocillins, including dehydrobutyrines, thiazoles, C-terminal decarboxylation, and the two previously unconfirmed dehydroalanines. Additionally, leader peptides have undergone extensive N-terminal degradation and the remaining leader peptide residues have been N-succinylated. These results identify TclM and its homologues in other thiazolyl peptide producing strains as the enzymes responsible for the trans-annular heteroannulation at core of this class of molecules.
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