Genome Mining of Amino Group Carrier Protein-Mediated Machinery: Discovery and Biosynthetic Characterization of a Natural Product with Unique Hydrazone Unit
Genome Mining of Amino Group Carrier Protein-Mediated Machinery: Discovery and Biosynthetic Characterization of a Natural Product with Unique Hydrazone Unit
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DOI：
10.1021/acschembio.6b00818
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发表时间：
2017-01-01
影响因子：
4
通讯作者：
Nishiyama, Makoto
中科院分区：
文献类型：
--
作者：
Matsuda, Kenichi;Hasebe, Fumihito;Nishiyama, Makoto
我们最近发现链霉菌菌株具有编码氨基载体蛋白（AmCP）的基因。AmCP参与了一种之前未被发现的非蛋白质原性氨基酸(25,6r)-二氨基-(5R,7)-二羟基七酸（DADH）的生物合成，DADH是合成含二肽的新型天然产物vazabitide a的核心化合物。我们使用聚合酶链反应（PCR）筛选来研究使用AmCP的生物合成机制的多样性；结果表明，编码AmCP的基因广泛分布于放线菌中。通过对Streptomyces sp. SoC090715LN-17中含有amcp的基因簇的异源表达，发现了一种新的天然产物556 -p1。通过光谱分析确定了556 -p1的结构；结果表明，556 -p1具有一个假定的dadh衍生分子作为核心，并且具有在天然产物中很少观察到的独特的腙单元。我们的结果为研究amcp介导的放线菌间未开发的生物合成途径和独特的腙单元的生物合成机制铺平了道路。
We recently revealed that a Streptomyces strain possesses the gene encoding amino group carrier protein (AmCP). AmCP is involved in the biosynthesis of a previously unidentified non-proteinogenic amino acid, (25,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH), which is a core compound for the synthesis of the dipeptide-containing novel natural product vazabitide A. We used polymerase chain reaction (PCR) screening to investigate the diversity of the biosynthetic machinery that uses AmCP; the results revealed that genes encoding AmCP are widely distributed among actinomycetes. The heterologous expression of the AmCP-containing gene cluster from Streptomyces sp. SoC090715LN-17 led to the discovery of s56-p1, a novel natural product. The structure of s56-p1 was determined by spectroscopic analysis; the results revealed that s56-p1 has a putative DADH-derived molecule as the core and also possesses a unique hydrazone unit that is rarely observed in natural products. Our results pave the way for investigations of unexploited AmCP-mediated biosynthesis routes among actinomycetes and of the biosynthetic mechanism of the unique hydrazone unit.