Characterization of the lnmKLM genes unveiling key intermediates for β-alkylation in leinamycin biosynthesis.

Characterization of the lnmKLM genes unveiling key intermediates for β-alkylation in leinamycin biosynthesis.
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DOI:
10.1021/ol102838y
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发表时间:
2011-02-04
期刊:
影响因子:
5.2
通讯作者:
Shen, Ben
Shen, Ben
中科院分区:
化学1区
文献类型:
--
作者:
Huang, Yong;Huang, Sheng-Xiong;Ju, Jianhua;Tang, Gongli;Liu, Tao;Shen, Ben

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莱那霉素(LNM,1)的生物合成涉及LnmKLM催化的聚酮中间体的β-烷基化。灭活lnmK、lnmL或lnmM得到突变菌株,其积累LNM K-1(2)、K-2(3)、K-3(4)和异构体LNM K-1′(5)、K-2′(6)和K-3′(7),其聚酮化合物来源通过[1- 13 C]乙酸钠的饲喂实验确定。这些发现证实了LnmKLM在1生物合成中的不可或缺性,并表明β-烷基化在与LNM聚酮化合物合酶结合时在生长的聚酮化合物中间体上进行。
Leinamycin (LNM, 1) biosynthesis is proposed to involve β-alkylation of the polyketide intermediate, catalyzed by LnmKLM. Inactivation of lnmK, lnmL, or lnmM afforded mutant strains that accumulated LNM K-1 (2), K-2 (3), K-3 (4), and isomers LNM K-1′ (5), K-2′ (6), and K-3′ (7) whose polyketide origin were established by feeding experiments with sodium [1-13C]acetate. These findings confirm the indispensability of LnmKLM in 1 biosynthesis and suggest that β-alkylation proceeds on the growing polyketide intermediate while bound to the LNM polyketide synthase.
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