An Acetyl-CoA-Gated Metabolic Checkpoint Links Precursor Supply to Cordycepin Biosynthesis in Cordyceps militaris

Current Issues in Molecular Biology 2026 Open access

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Authors: Hucheng Zhang, Dongqing Yang, Guowei Yang, Shuai Luo, Peng Lu, Guoli Xie, Yapeng Song, Jun Yang, Linying Liu, Haitao Fan, Wenyan Lao, Frank Vriesekoop
DOI: 10.3390/cimb48040370
Cited by: 2
References: 39

Abstract

high-yield GYS60 and low-yield GYS80 via comparative proteomics, Post-Translational Modification (PTM) mapping, and metabolomics. We identified an acetyl-CoA-gated checkpoint centered on O-methyltransferase CCM_06472, whose activity is modulated by Lys123 acetylation and Ser34 phosphorylation in a manner consistent with activation and inhibition. GYS60 hyperactivates the tricarboxylic acid (TCA) cycle and β-oxidation to generate a 4.1-fold acetyl-CoA surplus, 62% of which is channeled into cordycepin synthesis. A single K123Q acetylation-mimetic mutation boosted cordycepin titers by >4-fold in wild-type strains. This acetyl-CoA checkpoint reveals PTM-gated flux allocation as a key regulatory mechanism, providing a minimal-intervention strategy for engineering fungal cell factories.

Fields of Study & Subjects

Fungal Biology and Applications Polysaccharides and Plant Cell Walls Fungal and yeast genetics research

Publication details

Journal / source
Current Issues in Molecular Biology
Publisher
MDPI AG
Volume
48
Issue
4
Pages
370–370
Publication date
2 April 2026
Language
EN