Affiliation:
1. 0000 0004 1761 2484 grid.33763.32 Department Biochemical Engineering, School Chemical Engineering and Technology Tianjin University 300072 Tianjin China
2. 0000 0000 9389 5210 grid.412022.7 College of Biotechnology and Pharmaceutical Engineering Nanjing Tech University 211816 Nanjing China
3. 0000 0004 1798 2282 grid.410613.1 Laboratory for Advanced Technology in Environmental Protection of Jiangsu Province Yancheng Institute of Technology 224051 Yancheng China
4. 0000 0000 9389 5210 grid.412022.7 School of Pharmaceutical Sciences Nanjing Tech University 211816 Nanjing China
Abstract
Abstract
Metabolic profiling was used to discover mechanisms of increased pneumocandin B0 production in a high-yield strain by comparing it with its parent strain. Initially, 79 intracellular metabolites were identified, and the levels of 15 metabolites involved in six pathways were found to be directly correlated with pneumocandin B0 biosynthesis. Then by combining the analysis of key enzymes, acetyl-CoA and NADPH were identified as the main factors limiting pneumocandin B0 biosynthesis. Other metabolites, such as pyruvate, α-ketoglutaric acid, lactate, unsaturated fatty acids and previously unreported metabolite γ-aminobutyric acid were shown to play important roles in pneumocandin B0 biosynthesis and cell growth. Finally, the overall metabolic mechanism hypothesis was formulated and a rational feeding strategy was implemented that increased the pneumocandin B0 yield from 1821 to 2768 mg/L. These results provide practical and theoretical guidance for strain selection, medium optimization, and genetic engineering for pneumocandin B0 production.
Funder
National Natural Science Foundation of China
National High Technology Research and Development Program
Program for Innovative Research Team in University of Jiangsu Province
Natural Science Fund for Colleges and Universities in Jiangsu Province
Postgraduate Research and Practice Innovation Program of Jiangsu Province
Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture
Publisher
Oxford University Press (OUP)
Subject
Applied Microbiology and Biotechnology,Biotechnology,Bioengineering
Cited by
11 articles.
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