ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Synthetic Biology
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1616558
This article is part of the Research TopicAdvancements in microbial engineering for natural product synthesisView all articles
The effect on shikimate production by deleting iolR and metabolic engineering in PTS deficient Corynebacterium glutamicum strain
Provisionally accepted- Massachusetts Institute of Technology, Cambridge, United States
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Shikimate is a precursor to many high-value chemical derivatives. Several bacteria have been engineered to produce high titer of shikimate via non-phosphotransferase system (Non-PTS), but yet explores how the myo-inositol utilization transcription regulator (iolR) deletion affects the shikimate titer in phosphotransferase system (PTS) deficient strain. In this study, we engineered Corynebacterium glutamicum to produce shikimate in a PTS deficient strain with the deletion of iolR and improved shikimate production using a metabolic engineering approach. After the native shikimate kinase (aroK) and quinic acid/shikimate dehydronases (qusD) genes were deleted, shikimate was able to accumulate. Next, we increased shikimate production by eliminating byproducts. Furthermore, PTS was eliminated to improve phosphoenolpyruvate levels, however, both the cell growth rate and shikimate production were dramatically reduced. Hence, iolR was deleted to improve cell growth and shikimate production in the PTS deficient strain. In addition, we overexpressed genes in the glycolysis and shikimate pathways to increase shikimate production. The combination of the strategies resulted in a shikimate content of 0.76 mg/mg of DCW and a titer of 4.1 g/L in shake flask in C. glutamicum.
Keywords: Shikimate, PTS deficient, IolR, Corynebacterium glutamicum, Metabolic Engineering
Received: 23 Apr 2025; Accepted: 17 Jun 2025.
Copyright: © 2025 Ou, Swofford, Zhong-Johnson, Li and Sinskey. 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:
Cheng Li, Massachusetts Institute of Technology, Cambridge, United States
Anthony J. Sinskey, Massachusetts Institute of Technology, Cambridge, United States
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