Enhanced avermectin production by rational feeding strategies based on comparative metabolomics

Abstract:

[Objective] In order to reveal key metabolites and metabolic pathways of avermectin, comparative metabolomics approach was used to analyze the difference of key intracellular metabolites of Streptomyces avermitilis in different fermentation media. Then the rational feeding approach was used to enhance avermectin production.[Methods] Mycelial samples in M1 and M2 media were analyzed by GC-MS based comparative intracellular metabolomics. Based on the deficiency of relative metabolic pathways, single precursor supplement and combined precursors supplement were exerted, and the optimized medium M3 was obtained to enhance avermectin production.[Results] In total 232 intracellular metabolites were identified and 70 of them were accurately matched, and 21 metabolites influencing avermectin biosynthesis were finally verified by PCA and PLS analyses. Among them, lactic acid, pyruvic acid, succinic acid, threonine, isoleucine, valine and lipids determined the avermectin titer more obviously. When supplying with these precursors together to M2 at different time points, the titer increased by 10.4% from 5.36 g/L to 5.92 g/L.[Conclusion] The production of avermectin increased apparently with the help of comparative metabolomics analysis and rational feeding optimization. It also provides a new approach to enhance the yield of bioproducts.