文献类型：期刊文献

英文题名：Comparative Fluxome and Metabolome Analysis of Formate as an Auxiliary Substrate for Penicillin Production in Glucose-Limited Cultivation of Penicillium chrysogenum

作者：Wang, Guan[1];Wang, Xinxin[1];Wang, Tong[1];van Gulik, Walter[2];Noorman, Henk J.[3,4];Zhuang, Yingping[1];Chu, Ju[1];Zhang, Siliang[1]

机构：[1]ECUST, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Delft Univ Technol, Dept Biotechnol, Cell Syst Engn, Delft, Netherlands;[3]DSM Biotechnol Ctr, Delft, Netherlands;[4]Delft Univ Technol, Dept Biotechnol, Delft, Netherlands

年份：2019

卷号：14

期号：10

外文期刊名：BIOTECHNOLOGY JOURNAL

收录：;EI(收录号：20194207546652);WOS:【SCI-EXPANDED(收录号:WOS:000488962800014)】；

语种：英文

外文关键词：auxiliary substrates; chemostat; metabolomics; penicillin; Penicillium chrysogenum

摘要：During glucose-limited growth, a substantial input of adenosine triphosphate (ATP) is required for the production of beta-lactams by the filamentous fungus Penicillium chrysogenum. Formate dehydrogenase has been confirmed in P. chrysogenum for formate oxidation allowing an extra supply of ATP, and coassimilation of glucose and formate has the potential to increase penicillin production and biomass yield. In this study, the steady-state metabolite levels and fluxes in response to cofeeding of formate as an auxiliary substrate in glucose-limited chemostat cultures at the dilution rates (D) of both 0.03 h(-1) and 0.05 h(-1) are determined to evaluate the quantitative impact on the physiology of a high-yielding P. chrysogenum strain. It is observed that an equimolar addition of formate is conducive to an increase in both biomass yield and penicillin production at D = 0.03 h(-1), while this is not the case at D = 0.05 h(-1). In addition, a higher cytosolic redox status (NADH/NAD(+)), a higher intracellular glucose level, and lower penicillin productivity are only observed upon formate addition at D = 0.05 h(-1), which are virtually absent at D = 0.03 h(-1). In conclusion, the results demonstrate that the effect of formate as an auxiliary substrate on penicillin productivity in the glucose-limited chemostat cultivations of P. chrysogenum is not only dependent on the formate/glucose ratio as published before but also on the specific growth rate. The results also imply that the overall process productivity and quality regarding the use of formate should be further explored in an actual industrial-scale scenario.