title: Metabolic analysis reveals the amino acid responses of Streptomyces lydicus to pitching ratios during improving streptolydigin production.
abstract: Pitching ratio has been reported to impact not only on the primary metabolism, but also the secondary metabolism. Comparative metabolomics was used to explore the metabolic responses of Streptomyces lydicus E9 to pitching ratios (1, 10, and 30%, v/v). We identified more than 120 metabolites involved in glycolysis, tricarboxylic acid cycle, and amino acid and secondary metabolism, of which there are significant differences in the quantified 32 metabolites under different pitching ratios by gas chromatography coupled to time-of-flight mass spectrometry. The intracellular levels of most amino acids (e.g., valine, alanine, and isoleucine) declined with the increases of pitching ratios. Especially, the relative abundances of glutamate and proline were not only decreased with the increases of pitching rations, but also had much low level at stages II and III, which might be related to the significant enhancement in streptolydigin of S. lydicus E9 under 30% high pitching ratio. Moreover, principal component analysis revealed that eight metabolites, including glucopyranoside, maltose, cAMP, glycine, proline, lysine, isoleucine, and valine, were considered as potential biomarkers to distinguish the influences of pitching ratios on streptolydigin production. Further investigations demonstrated that the additions of exogenous glutamate and proline (100 mgL⁻¹) enhanced significantly the accumulation of streptolydigin, indicating that glutamate was the synthetic precursor of streptolydigin, while proline in S. lydicus E9 was converted into glutamate and consequently improved streptolydigin biosynthesis. Therefore, these findings provide new insights into the amino acid responses of S. lydicus E9 to pitching ratios and provide potential strategies to improve streptolydigin production.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, P.O. Box 6888, Tianjin 300072, People's Republic of China. jscheng@tju.edu.cn
authors.forename: Jing-Sheng
authors.initials: JS
authors.lastname: Cheng
authors.forename: Ying-Quan
authors.initials: YQ
authors.lastname: Liang
authors.forename: Ming-Zhu
authors.initials: MZ
authors.lastname: Ding
authors.forename: Shao-Fei
authors.initials: SF
authors.lastname: Cui
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Lv
authors.forename: Ying-Jin
authors.initials: YJ
authors.lastname: Yuan
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000617:Aminoglycosides / Q000096:biosynthesis*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D008401:Gas Chromatography-Mass Spectrometry; D055442:Metabolome; D013302:Streptomyces / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C100307:streptolydigin