Biosynthetic Origin of the Antibiotic Cyclocarbamate Brabantamide A (SB‐253514) in Plant‐Associated Pseudomonas.
Biosynthetic Origin of the Antibiotic Cyclocarbamate Brabantamide A (SB‐253514) in Plant‐Associated Pseudomonas.
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DOI：
10.1002/cbic.201300527
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发表时间：
2014-01
期刊：
影响因子：
3.2
通讯作者：
Yvonne Schmidt;Menno van der Voort;M. Crüsemann;J. Piel;Michaele Josten;H. Sahl;Henrike Miess;J. Raaijmakers;H. Gross
中科院分区：
文献类型：
--
作者：
Yvonne Schmidt;Menno van der Voort;M. Crüsemann;J. Piel;Michaele Josten;H. Sahl;Henrike Miess;J. Raaijmakers;H. Gross
在我们从假单胞菌中发现新的抗生素脂肽的基因组计划框架内，brabantamides A-C从植物相关假单胞菌sp. SH‐C52中分离出来。Brabantamides A-C对革兰氏阳性病原菌具有中高的体外活性。它们的共同结构是独特的，因为它们含有一个5,5 -双环氨基甲酸酯支架。本研究采用生物信息学、同位素标记前体的饲养实验以及生物合成途径中编码酶的体内和体外功能分析相结合的方法研究了brabantamide A （SB‐253514）的生物合成。这些研究推导出了brabantamide A的所有生物合成构建块，并揭示了这种代谢物的一个不寻常的特征：它的生物合成是通过最初形成的线性二脂肽进行的，随后被一种新的FAD依赖性Baeyer-Villiger单加氧酶重新排列。
Within the framework of our genome‐based program to discover new antibiotic lipopeptides from Pseudomonads, brabantamides A–C were isolated from plant‐associated Pseudomonas sp. SH‐C52. Brabantamides A–C displayed moderate to high in vitro activities against Gram‐positive bacterial pathogens. Their shared structure is unique in that they contain a 5,5‐bicyclic carbamate scaffold. Here, the biosynthesis of brabantamide A (SB‐253514) was studied by a combination of bioinformatics, feeding experiments with isotopically labelled precursors and in vivo and in vitro functional analysis of enzymes encoded in the biosynthetic pathway. The studies resulted in the deduction of all biosynthetic building blocks of brabantamide A and revealed an unusual feature of this metabolite: its biosynthesis occurs via an initially formed linear di‐lipopeptide that is subsequently rearranged by a novel FAD‐dependent Baeyer–Villiger monooxygenase.