New Aminocoumarins from the Rare Actinomycete Catenulispora acidiphila DSM 44928: Identification, Structure Elucidation, and Heterologous Production
New Aminocoumarins from the Rare Actinomycete Catenulispora acidiphila DSM 44928: Identification, Structure Elucidation, and Heterologous Production
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DOI：
10.1002/cbic.201300712
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发表时间：
2014-03
期刊：
影响因子：
3.2
通讯作者：
J. Zettler;Haiyang Xia;Nadja Burkard;A. Kulik;S. Grond;L. Heide;A. Apel
中科院分区：
文献类型：
--
作者：
J. Zettler;Haiyang Xia;Nadja Burkard;A. Kulik;S. Grond;L. Heide;A. Apel
基因组挖掘导致在罕见的放线菌嗜酸链孢菌DSM 44928中发现一个新的氨基香豆素基因簇。序列分析揭示了参与氨基香豆素部分的输出/抗性、调节和生物合成及其卤化的puerectin基因的存在，以及迄今为止功能未知的几个基因。从C. cacibiocin A和B的培养液中鉴定出两种新的氨基香豆素类化合物。嗜酸菌。推定的基因簇在天蓝色链霉菌M1152中的异源表达证实了该簇负责钙霉素的生物合成。此外，通过异源表达和筛选不同的培养基，可以从C中4.9 mg L-1的初始产量增加cacibiocins的总产量水平。acidophila的浓度为60 mg L-1。天蓝色M1152.通过HR-MS和NMR分析，发现cacibiocin A含有通过酰胺键与吡咯-2，5-二羧酸连接的3-氨基-4，7-二羟基香豆素部分。后一种结构基序以前在任何天然化合物中均未被鉴定。此外，钙霉素B在氨基香豆素部分的6′和8′位含有两个氯原子。
Genome mining led to the discovery of a novel aminocoumarin gene cluster in the rare actinomycete Catenulispora acidiphila DSM 44928. Sequence analysis revealed the presence of genes putatively involved in export/resistance, regulation, and biosynthesis of the aminocoumarin moiety and its halogenation, as well as several genes with so far unknown function. Two new aminocoumarins, cacibiocin A and B, were identified in the culture broth of C. acidiphila. Heterologous expression of the putative gene cluster in Streptomyces coelicolor M1152 confirmed that this cluster is responsible for cacibiocin biosynthesis. Furthermore, total production levels of cacibiocins could be increased by heterologous expression and screening of different culture media from an initial yield of 4.9 mg L−1 in C. acidiphila to 60 mg L−1 in S. coelicolor M1152. By HR‐MS and NMR analysis, cacibiocin A was found to contain a 3‐amino‐4,7‐dihydroxycoumarin moiety linked by an amide bond to a pyrrole‐2,5‐dicarboxylic acid. The latter structural motif has not been identified previously in any natural compound. Additionally, cacibiocin B contains two chlorine atoms at positions 6′ and 8′ of the aminocoumarin moiety.