文献类型：期刊文献

英文题名：A novel pH-precursor-glucose synergic control strategy for dinactin biosynthesis by an arctic actinornycete Streptomyces sp.

作者：He, Hao[1];Xue, Ying[1];Xu, Ning[1];Yin, Ying[1];Lu, Jian[1];Cai, Menghao[1];Zhang, Yuanxing[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Shanghai Collaborat Innovat Ctr Biomfg, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2016

卷号：51

期号：12

起止页码：1911

外文期刊名：PROCESS BIOCHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000390733500003)】；

基金：This study was financially supported by the National High Technology Research and Development Program of China (2012AA092105), National Natural Science Foundation of China (41306121), Fundamental Research Funds for the Central Universities (22A201514040), and Special Project for "Significant New Drugs Development" from the Ministry of National Science and Technology (2012ZX09102101). The authors thank Prof. Bo Chen, Polar Research Institute of China, for providing the strain and general assistance. The authors also sincerely thank Dr Ke Na, Shanghai Institute of Pharmaceutical Industry, for providing some dinactin standard. Finally, the authors thank Prof. Qiang Hua, East China University of Science and Technology, for providing the strain E. coli ET12567 and plasmid pIB139.

语种：英文

外文关键词：Dinactin; pH-precursor-glucose regulation nonS; Succinate

摘要：Dinactin, a macrotetrolide antibiotic produced by Streptomyces sp. R-527F, has attracted much attention in the ongoing pharmaceutical research because of its potential immunosuppressive properties. The aim of this study was to develop a robust fermentation platform for dinactin production. In the first step, we found that dinactin biosynthesis was significantly affected by pH that could be optimally controlled at 5.2-5.5. In this pH-regulated condition, dinactin production reached 124mg/L, which was 1.8-fold of the control. Subsequently, we developed a feeding strategy based on the precursor sodium succinate in combination with pH control and obtained dinactin production of 291 mg/L, which was 4.22-fold of the original control. Furthermore, glucose-feeding strategies were designed based on the pH precursor regulation results, allowing dinactin production of 343 mg/L, which was 4.97-fold compared to the original conditions. Finally, the establishment of an engineered strain overexpressing the nonS gene encoding for the closure of the tetrahydrofuran ring in dinactin biosynthesis and its cultivation on the pH-precursor-glucose regulation platform yielded 382 mg/L dinactin, which further increased the yield by 11% as compared to the wild type under the same conditions. The designed bioprocess strategy holds the potential for large-scale production of dinactin. (C) 2016 Elsevier Ltd. All rights reserved.