Avenolide, a Streptomyces hormone controlling antibiotic production in Streptomyces avermitilis
Avenolide, a Streptomyces hormone controlling antibiotic production in Streptomyces avermitilis
复制标题
DOI：
10.1073/pnas.1113908108
复制
发表时间：
2011-09-27
影响因子：
11.1
通讯作者：
Nihira, Takuya
中科院分区：
文献类型：
--
作者：
Kitani, Shigeru;Miyamoto, Kiyoko T.;Nihira, Takuya
链霉菌属的革兰氏阳性菌是工业上重要的微生物，生产约70%的商业上重要的抗生素。这些化合物的产生通常由低分子量的细菌激素（称为自体调节剂）调节。虽然60%的链霉菌菌株可能使用。-丁内酯型分子作为自身调节剂，一些使用呋喃型分子，但对该属许多其他成员用于调节抗生素产生的信号分子知之甚少。在这里，我们从阿维菌链霉菌中纯化了一个信号分子（avenolide），通过光谱分析和化学合成确定了它的结构，包括立体化学，为(4S, 10R)-10-羟基-10-甲基-9-氧十二烷基-2-en-1,4-olide，一类链霉菌的自动调节剂。阿维内酯是引发阿维菌素生产所必需的，在纳摩尔浓度下有效，最低有效浓度为4 nM。阿维霉菌的aco基因编码一种酰基辅酶a氧化酶，是绿烯内酯生物合成所必需的，同源基因也存在于传统链霉菌、加纳链霉菌和灰褐色链霉菌中，这表明丁烯内酯型自调节因子可能是链霉菌中广泛存在的另一类参与调节抗生素生产的自调节因子。
Gram-positive bacteria of the genus Streptomyces are industrially important microorganisms, producing >70% of commercially important antibiotics. The production of these compounds is often regulated by low-molecular-weight bacterial hormones called autoregulators. Although 60% of Streptomyces strains may use.-butyrolactone-type molecules as autoregulators and some use furan-type molecules, little is known about the signaling molecules used to regulate antibiotic production in many other members of this genus. Here, we purified a signaling molecule (avenolide) from Streptomyces avermitilis-the producer of the important anthelmintic agent avermectin with annual world sales of $ 850 million-and determined its structure, including stereochemistry, by spectroscopic analysis and chemical synthesis as (4S, 10R)-10-hydroxy-10methyl-9-oxo-dodec-2-en-1,4-olide, a class of Streptomyces autoregulator. Avenolide is essential for eliciting avermectin production and is effective at nanomolar concentrations with a minimum effective concentration of 4 nM. The aco gene of S. avermitilis, which encodes an acyl-CoA oxidase, is required for avenolide biosynthesis, and homologs are also present in Streptomyces fradiae, Streptomyces ghanaensis, and Streptomyces griseoauranticus, suggesting that butenolide-type autoregulators may represent a widespread and another class of Streptomyces autoregulator involved in regulating antibiotic production.