文献类型：期刊文献

英文题名：Nonstationary 13C metabolic flux analysis reveals cryptic phenylacetic acid catabolism in glucose-limited Penicillium chrysogenum chemostat cultures

作者：Zhao, Jiachen[1];Lin, Wenli[1];Yang, Jing[1];Wang, Gaoya[1];Wang, Yongbo[1];Chang, Mengyuan[1];Wang, Xueting[1];Muawiya, Muhammad Alkali[1];Wang, Zejian[1];Zhuang, Yingping[1,2];Wang, Guan[1,2]

机构：[1]East China Univ Sci & Technol ECUST, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Qingdao New Energy Shandong Lab, Qingdao, Peoples R China

年份：2026

卷号：440

外文期刊名：BIORESOURCE TECHNOLOGY

收录：;EI(收录号：20254119297183);WOS:【SCI-EXPANDED(收录号:WOS:001592688900002)】；

基金：This research was funded by the National Key R & D Program of China (Grant no. 2021YFC2101000) , the Taishan Scholars Program of Shan-dong Province (Grant no. tspn202408281) and the Fundamental Research Funds for the Central Universities (Grant No. JKF01241708) .

语种：英文

外文关键词：Overflow control; Feedback control; Penicillin; PAA degradation; Metabolomics; Isotope tracing

摘要：Penicillium chrysogenum is the key industrial microorganism for penicillin production, and understanding its metabolic regulation is crucial for optimizing yields. While different chemostat strategies influence fermentation outcomes, the underlying metabolic mechanisms remain poorly understood. To address this, non-stationary 13C metabolic flux analysis (13C-MFA) was employed combined with quantitative metabolite profiling to investigate the physiological response of P. chrysogenum Wisconsin 54-1255 under both overflow- and feedback-controlled chemostats. Under overflow control, extracellular glucose concentrations were reduced to one-fifth of feedback levels, while the intracellular amount of glucose doubled. Concomitantly, the specific uptake rate of phenylacetic acid (PAA) increased twofold, while penicillin productivity decreased by 25%. Importantly, 13C-MFA revealed a shift towards a benzoic acid degradation pathway for PAA, sustaining the TCA cycle flux comparable to those under feedback control. These findings underscore the uncharacterized role of PAA catabolism in maintaining central carbon metabolism under overflow control, offering insights and strategies for further enhancing industrial penicillin production.