ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.

Sec. Synthetic Biology

Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1621955

This article is part of the Research TopicBiosynthesis of Terpenoids: Mechanism, Engineering, and IndustrializationView all articles

Enabling and improving trans-nerolidol production by Corynebacterium glutamicum: Combining metabolic engineering and trace elements medium refinement

Provisionally accepted
Jan  SeegerJan SeegerStella  LohoffStella LohoffFabian  SchmitfranzFabian SchmitfranzNadja Alina  HenkeNadja Alina HenkeVolker  F. WENDISCHVolker F. WENDISCH*
  • Bielefeld University, Bielefeld, Germany

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

Terpenes are biomolecules of significant industrial relevance, with applications in pharmaceuticals, cosmetics, and the food industry. Their biotechnological production is emerging, with Corynebacterium glutamicum, a Gram-positive bacterium traditionally employed for large-scale amino acid production, serving as a promising host. While metabolic engineering strategies have been extensively applied to enhance terpene titers in C. glutamicum, the role of medium composition, particularly trace elements, remains underexplored. In this study, the impact of trace element composition on trans-nerolidol production by engineered C. glutamicum was investigated. A Design of Experiments (DoE) approach identified MgSO4 as a critical factor, and the refined trace element composition led to a 34% increase in trans-nerolidol production. Further metabolic engineering efforts resulted in a final titer of 28.1 mg L -1 . Subsequent fed-batch fermentation achieved a transnerolidol titer of 0.41 g L -1 , representing the highest reported sesquiterpene titer being produced by C. glutamicum to date. Additionally, the refined trace element composition was successfully applied to patchoulol-and (+)-valencene-producing strains, leading to production increases of 15% and 72%, respectively. These findings demonstrate that trace element refinement and metabolic engineering act as complementary strategies for enhancing terpene production in a microbial production host.

Keywords: Corynebacterium glutamicum, Trans-nerolidol, Terpenes, Design of Experiment, Media optimization, Metabolic Engineering

Received: 02 May 2025; Accepted: 06 Jun 2025.

Copyright: © 2025 Seeger, Lohoff, Schmitfranz, Henke and WENDISCH. 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: Volker F. WENDISCH, Bielefeld University, Bielefeld, Germany

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.