State Key Laboratory of Bioreactor Engineering, National Research Center for Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
J Proteomics. 2013 Feb 21;79:1-12. doi: 10.1016/j.jprot.2012.11.012. Epub 2012 Nov 29.
An industrial mutant of Streptomyces avermitilis produced avermectin at a high level in industrial complex culture medium. However, almost no avermectin was detected in the cultures of tryptone soya broth (TSB). Its wild-type strain could not synthesize avermectin. To elucidate the regulatory mechanism about avermectin production, proteomic analysis of S. avermitilis was carried out. Results showed that during avermectin biosynthesis, fatty acid metabolism and TCA cycle were repressed. Partial enrichment of glycolytic pathway indicated the critical role of glucose catabolism during avermectin biosynthesis. Some enriched enzymes in amino acid metabolic pathways (glnA, leuC) confirmed the leucine as the possible precursor of avermectin. Highly expressed stress or stress-related proteins indicated a global regulation mechanism at the onset of avermectin production. And highly expressed morphology control proteins revealed an association between hyphal morphology and avermectin production. Further, this study proofed strengthened capability to utilize carbon and nitrogen source in the industrial strain. Some stress or stress-related proteins (eshA, clpC, dnaK and grpE) expressed at low level in the industrial strain cultivated in non-production medium (lower than that in the wild-type strain), but these highly expressed at the onset of avermectin production. More sensible response to environmental stress may be responsible for it.
阿维链霉菌的工业突变株能够在复杂的工业培养基中高水平地产生阿维菌素,而在胰蛋白胨大豆肉汤(TSB)中几乎检测不到阿维菌素。其野生型菌株不能合成阿维菌素。为了阐明阿维菌素产生的调控机制,对阿维链霉菌进行了蛋白质组学分析。结果表明,在阿维菌素生物合成过程中,脂肪酸代谢和 TCA 循环受到抑制。部分糖酵解途径的富集表明葡萄糖代谢在阿维菌素生物合成过程中起着关键作用。一些在氨基酸代谢途径中富集的酶(glnA、leuC)证实了亮氨酸是阿维菌素的可能前体。高度表达的应激或应激相关蛋白表明在阿维菌素产生时存在全局调控机制。高度表达的形态控制蛋白表明菌丝形态与阿维菌素产生之间存在关联。此外,这项研究证明了工业菌株在利用碳氮源方面的能力得到了增强。一些应激或应激相关蛋白(eshA、clpC、dnaK 和 grpE)在非生产培养基(低于野生型菌株)中培养的工业菌株中低水平表达,但在阿维菌素产生时高度表达。对环境应激的更敏感反应可能是造成这种情况的原因。