Comparative metabolomics reveals the mechanism of avermectin production enhancement by S-adenosylmethionine
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It was found that S-adenosylmethionine (SAM) could effectively improve avermectin titer with 30–60 μg/mL addition to FH medium. To clearly elucidate the mechanism of SAM on intracellular metabolites of Streptomyces avermitilis, a GC–MS-based comparative metabolomics approach was carried out. First, 230 intracellular metabolites were identified and 14 of them remarkably influenced avermectin biosynthesis were discriminative biomarkers between non-SAM groups and SAM-treated groups by principal components analysis (PCA) and partial least squares (PLS). Based on further key metabolic pathway analyses, these biomarkers, such as glucose, oxaloacetic acid, fatty acids (in soybean oil), threonine, valine, and leucine, were identified as potentially beneficial precursors and added in medium. Compared with single-precursor feeding, the combined feeding of the precursors and SAM markedly increased the avermectin titer. The co-feeding approach not only directly verified our hypothesis on the mechanism of SAM by comparative metabolomics, but also provided a novel strategy to increase avermectin production.
KeywordsAvermectin S-adenosylmethionine Comparative metabolomics Metabolites Rational feeding
This work was financially supported by the National Basic Research Program (973 Program) of China (2013CB734004), and the Natural Science Foundation of China (31370075, 31471725, 61603273), and the Youth Innovation Fund of Tianjin University of Science and Technology of China (2014CXLG28). We also appreciate Dr. Arnold L. Demain for his valuable advice with the manuscript, Dr. Lixin Zhang for providing the experimental strain and Mr. Gang Guo for his technical support.
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