文献类型：期刊文献

英文题名：Quantitative metabolomics and metabolic flux analysis reveal impact of altered trehalose metabolism on metabolic phenotypes of Penicillium chrysogenum in aerobic glucose-limited chemostats

作者：Wang, Guan[1];Zhao, Junfei[1];Wang, Xinxin[1];Wang, Tong[1];Zhuang, Yingping[1];Chu, Ju[1];Zhang, Siliang[1];Noorman, Henk J.[2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]DSM Biotechnol Ctr, Delft, Netherlands;[3]Delft Univ Technol, Dept Biotechnol, Delft, Netherlands

年份：2019

卷号：146

起止页码：41

外文期刊名：BIOCHEMICAL ENGINEERING JOURNAL

收录：;EI(收录号：20191006612613);WOS:【SCI-EXPANDED(收录号:WOS:000466999900005)】；

基金：This work was financially subsidized by NWO-MoST Joint Program, Grant number, 2013DFG32630, the 111 Project (B18022), the National key research and development program, 2017ZX7402003, and the Fundamental Research Funds for the Central Universities, 22221818014.

语种：英文

外文关键词：Chemostat; Genome-scale metabolic model; Metabolomics; Penicillium chrysogenum; Trehalose metabolism; Metabolic flux analysis

摘要：In Penicillium chrysogenum, it has been observed that turnover of storage carbohydrates (trehalose, mannitol, arabitol, erythritol and glycogen) resulting in an extra ATP expenditure might partly account for the reduced penicillin productivity under dynamic cultivation conditions. In this work, Penicillium chrysogenum mutants with altered trehalose metabolism were constructed using the Agrobacterium-mediated transformation method. It was observed that impaired trehalose biosynthesis did not result in growth arrest and change of glucose sensitivity to high glucose levels, but negatively influenced the sporulation. Compared with the original strain, in glucose-limited chemostat cultures, the biomass yield on glucose and energy efficiency were slightly enhanced; however, the penicillin productivity was significantly lowered in the trehalose mutant strains. Comparison with a high-yielding P. chrysogenum strain revealed that the original and mutant strains had a lower glucose uptake capacity but higher intracellular levels of free amino acids. Flux estimates through the central carbon metabolism showed distinctive difference in the upper part of the glycolysis and in the pentose phosphate pathway but comparable flux through the TCA cycle. Combining, the striking phenotypic effects observed in the trehalose mutants of P. chrysogenum indicated that trehalose metabolism plays an important role in metabolic regulation and is central to maintaining higher penicillin productivity under glucose-limited chemostat cultures.