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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Microbiotechnology

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1669985

This article is part of the Research TopicGreen Biomanufacturing by Industrial Microorganisms: Precise Regulation and System OptimizationView all articles

Combinatorial Mutagenesis and Fermentation Optimization Biotechnologies Synergistically Enhance Monacolin K Content in Functional Red Yeast Rice

Provisionally accepted
Zhengyan  WuZhengyan Wu1Chan  ZhangChan Zhang2Qing  LiuQing Liu1Song  ZhangSong Zhang1Jun  LiuJun Liu1*Qi  YangQi Yang1Dong  LuDong Lu3Xiang  ZhouXiang Zhou3*
  • 1Central South University of Forestry and Technology, Changsha, China
  • 2Beijing Technology and Business University, Beijing, China
  • 3Institute of Modern Physics Chinese Academy of Sciences, Lanzhou, China

The final, formatted version of the article will be published soon.

This study aimed to improve the content of Monacolin K (MK), a cholesterollowering secondary metabolite, in red yeast rice by integrating advanced mutagenesis and fermentation optimization strategies. Combined atmospheric room-temperature plasma and heavy-ion radiation mutagenesis was performed to obtain a mutant M. purpureus CSUFT-1, which exhibited a remarkable 1.67-fold increase in MK production during solid-sate fermentation (SSF) compared to the original strain.Through refinement of SSF parameters, specifically, adding optimized corn steep liquor adjuvant solution [60% (v/v) corn steep liquor, pH modulation at 5, 3 g/L of MgSO4•7H₂O, 1.5 g/L of KH2PO4] with 20% (v/w) of injection volume, the MK yield was significantly amplified to 32.71 mg/g on day 28. Scale-up experiments confirmed the robustness of the optimized process, with MK production stabilizing approximately at 24.66 mg/g. RT-qPCR results showed that seven key genes, including mokC (6.8-fold upregulation) and mokF (22-fold upregulation), were significantly activated during the early stage of fermentation to drive precursor synthesis, only mokE gene exhibited the sustained overexpression in M. purpureus CSUFT-1 during the entire SSF. This study demonstrates a synergistic strategy integrating combinatorial mutagenesis with bioprocess optimization, providing both microbial resource and technical protocol for industrial-scale high MK yield.

Keywords: M. purpureus, Monacolin K, Mutagenesis, solid-state fermentation, RT-qPCR

Received: 21 Jul 2025; Accepted: 04 Aug 2025.

Copyright: © 2025 Wu, Zhang, Liu, Zhang, Liu, Yang, Lu and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Jun Liu, Central South University of Forestry and Technology, Changsha, China
Xiang Zhou, Institute of Modern Physics Chinese Academy of Sciences, Lanzhou, China

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