Reconstruction of a Genome-Scale Metabolic Model for Aspergillus oryzae Engineered Strain: A Potent Computational Tool for Enhancing Cordycepin Production
1
Issued Date
2025-07-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-105011849723
Journal Title
International Journal of Molecular Sciences
Volume
26
Issue
14
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.26 No.14 (2025)
Suggested Citation
Raethong N., Jeennor S., Anantayanon J., Wannawilai S., Vongsangnak W., Laoteng K. Reconstruction of a Genome-Scale Metabolic Model for Aspergillus oryzae Engineered Strain: A Potent Computational Tool for Enhancing Cordycepin Production. International Journal of Molecular Sciences Vol.26 No.14 (2025). doi:10.3390/ijms26146906 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111496
Title
Reconstruction of a Genome-Scale Metabolic Model for Aspergillus oryzae Engineered Strain: A Potent Computational Tool for Enhancing Cordycepin Production
Corresponding Author(s)
Other Contributor(s)
Abstract
Cordycepin, a bioactive adenosine analog, holds promise in pharmaceutical and health product development. However, large-scale production remains constrained by the limitations of natural producers, Cordyceps spp. Herein, we report the reconstruction of the first genome-scale metabolic model (GSMM) for a cordycepin-producing strain of recombinant Aspergillus oryzae. The model, iNR1684, incorporated 1684 genes and 1947 reactions with 93% gene-protein-reaction coverage, which was validated by the experimental biomass composition and growth rate. In silico analyses identified key gene amplification targets in the pentose phosphate and one-carbon metabolism pathways, indicating that folate metabolism is crucial for enhancing cordycepin production. Nutrient optimization simulations revealed that chitosan, D-glucosamine, and L-aspartate preferentially supported cordycepin biosynthesis. Additionally, a carbon-to-nitrogen ratio of 11.6:1 was identified and experimentally validated to maximize production, higher than that reported for Cordyceps militaris. These findings correspond to a faster growth rate, enhanced carbon assimilation, and broader substrate utilization by A. oryzae. This study demonstrates the significant role of GSMM in uncovering rational engineering strategies and provides a quantitative framework for precision fermentation, offering scalable and sustainable solutions for industrial cordycepin production.