文献类型：期刊文献

英文题名：Ammonium sulfate supplementation enhances erythromycin biosynthesis by augmenting intracellular metabolism and precursor supply in Saccharopolyspora erythraea

作者：Yuan, Yujie[1];Xu, Feng[1];Ke, Xiang[1];Lu, Ju[1];Huang, Mingzhi[1];Chu, Ju[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2023

卷号：46

期号：9

起止页码：1303

外文期刊名：BIOPROCESS AND BIOSYSTEMS ENGINEERING

收录：;EI(收录号：20232714342554);WOS:【SCI-EXPANDED(收录号:WOS:001017659700001)】；

基金：AcknowledgementsThis work was financially supported by the National Key Research and Development Program of China (Grant No. 2019YFA0904300), National Natural Science Foundation of China (Grant No. 32071461), and the National Key Research and Development Program of China (Grant No. 2018YFA0900300).

语种：英文

外文关键词：Saccharopolyspora erythraea; Erythromycin production; Ammonium sulfate; Targeted metabolomics; Metabolic flux analysis; Cellular metabolic mechanism

摘要：In this study, the cellular metabolic mechanisms regarding ammonium sulfate supplementation on erythromycin production were investigated by employing targeted metabolomics and metabolic flux analysis. The results suggested that the addition of ammonium sulfate stimulates erythromycin biosynthesis. Targeted metabolomics analysis uncovered that the addition of ammonium sulfate during the late stage of fermentation resulted in an augmented intracellular amino acid metabolism pool, guaranteeing an ample supply of precursors for organic acids and coenzyme A-related compounds. Therefore, adequate precursors facilitated cellular maintenance and erythromycin biosynthesis. Subsequently, an optimal supplementation rate of 0.02 g/L/h was determined. The results exhibited that erythromycin titer (1311.1 & mu;g/mL) and specific production rate (0.008 mmol/gDCW/h) were 101.3% and 41.0% higher than those of the process without ammonium sulfate supplementation, respectively. Moreover, the erythromycin A component proportion increased from 83.2% to 99.5%. Metabolic flux analysis revealed increased metabolic fluxes with the supplementation of three ammonium sulfate rates.