Manipulation of pathway regulation in Streptomyces globisporus for overproduction of the enediyne antitumor antibiotic C-1027.
Manipulation of pathway regulation in Streptomyces globisporus for overproduction of the enediyne antitumor antibiotic C-1027.
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DOI：
10.1038/ja.2010.55
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发表时间：
2010-08
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影响因子：
--
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操纵通路调控是增加特定次级代谢物产生的有效策略。在这里，我们通过操纵C-1027生物合成基因簇中的三个调节基因，sgcR1， sgcR2和sgcR3，成功地提高了烯二炔抗肿瘤抗生素C-1027和七肽（C-1027途径的早期代谢物）的生产。SgcR3先前已被确定为激活剂，我们现在提出SgcR1和SgcR2也是正调节因子，基于它们对全球链霉菌中庚烯和C-1027的滴度和/或时间的上调作用。具体来说，与野生型菌株相比，sgcR1的过表达显著提高了七烯（约5倍）和C-1027（2- 3倍）的产量。然而，heptaene和C-1027的效价并没有因为同时过表达这三种激活因子而升高，这说明了C-1027生物合成途径调控的复杂性。利用七烯作为一种易于识别和独特的指标来快速检测烯二醛的可能性也进行了评估。
Manipulation of pathway regulation is an efficient strategy to increase specific secondary metabolite production. Here we successfully improved production of both the enediyne antitumor antibiotic C-1027 and a heptaebe, an early metabolite of the C-1027 pathway, by manipulating the three regulatory genes, sgcR1, sgcR2, and sgcR3, within the C-1027 biosynthetic gene cluster. SgcR3 has previously been established as an activator, and we now propose that SgcR1 and SgcR2 are also positive regulators based on their up-regulation effects on titer and/or timing of heptaene and C-1027 production in Streptomyces globisporus. Specifically, overexpression of sgcR1 significantly improved production of the heptaene (about 5-fold) and C-1027 (2- to 3-fold) compared to the wild-type strain. However, the titers of heptaene and C-1027 were not increased by overexpressing all three activators together, underscoring the complexity of C-1027 biosynthetic pathway regulation. The possibility of exploiting the heptaene as a readily identifiable and unique indicator for rapidly detecting enediyne production was also assessed.
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影响因子：
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