title: Comparative metabolomics reveals the mechanism of avermectin production enhancement by S-adenosylmethionine.
abstract: 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.
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Tian
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hu
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
authors.forename: Depei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Computer Sciences and Information Engineering, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Logistics Service Group, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, People's Republic of China. gaoqiang@tust.edu.cn.
authors.forename: Qiang
authors.identifier: 0000-0003-4075-7115
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D005227:Fatty Acids / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000378:metabolism; D055432:Metabolomics; D025341:Principal Component Analysis; D012436:S-Adenosylmethionine / Q000378:metabolism*; D013302:Streptomyces / Q000378:metabolism
chemical_list: D000596:Amino Acids; D003470:Culture Media; D005227:Fatty Acids; D007559:Ivermectin; C019264:avermectin; D002244:Carbon; D012436:S-Adenosylmethionine
keywords: Avermectin; Comparative metabolomics; Metabolites; Rational feeding; S-adenosylmethionine