文献类型：期刊文献

英文题名：Enhancement of riboflavin production in Bacillus subtilis via in vitro and in vivo metabolic engineering of pentose phosphate pathway

作者：Zhang, Mengxue[1];Zhao, Xingcong[1];Chen, Xi[1];Li, Mingyue[2];Wang, Xuedong[1]

机构：[1]East China Univ Sci & Technol, New World Inst Biotechnol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Univ Calif Davis, Coll Biol Sci, Davis, CA 95616 USA

年份：2021

卷号：43

期号：12

起止页码：2209

外文期刊名：BIOTECHNOLOGY LETTERS

收录：;EI(收录号：20214010984809);WOS:【SCI-EXPANDED(收录号:WOS:000703355400001)】；

基金：This study was funded by the projects of the National Key Research and Development Program of China (Grant No. 2019YFC1805200).

语种：英文

外文关键词：Bacillus subtilis; Carbon metabolism flux; Pentose phosphate pathway; Riboflavin; Sodium gluconate

摘要：Objectives The production of riboflavin with Bacillus subtilis, is an established process, however it is yet to be fully optimized. The aim of this study was to explore how riboflavin yields can be improved via in vitro and in vivo metabolic engineering modification of the pentose phosphate pathway (PPP). Results In vitro, glucose was replaced with sodium gluconate to enhance PPP. Flask tests showed that the riboflavin titer increased from 0.64 to 0.87 g/L. The results revealed that the direct use of sodium gluconate could benefit riboflavin production. In vivo, gntP (encoding gluconate permease) was overexpressed to improve sodium gluconate uptake. The riboflavin titer reached 1.00 g/L with the mutant B. subtilis RF01. Ultimately, the fermentation verification of the engineered strain was carried out in a 7-L fermenter, with the increased riboflavin titer validating this approach. Conclusions The combination of metabolic engineering modifications in vitro and in vivo was confirmed to promote riboflavin production efficiently by increasing PPP and has great potential for industrial application. Graphic abstract This work is aimed to explore how to improve the riboflavin yield by the rational renovation of the pentose phosphate pathway (PPP). In vitro, metabolic engineering mainly uses sodium gluconate as a carbon source instead of glucose, and in vivo, metabolic engineering mainly includes the overexpression of sodium gluconate utility-related genes. The effect of sodium gluconate on cell growth, riboflavin production was investigated in the flasks and fermenter scale.