Light-Exposed Metabolic Responses of Cordyceps militaris through Transcriptome-Integrated Genome-Scale Modeling.

Area of Science:

• Biotechnology
• Metabolic Engineering
• Mycology

Background:

• Genome-scale metabolic models (GSMM) offer insights into microbial metabolism.
• Standard GSMMs have limitations in predicting responses to environmental factors like light.
• Cordyceps militaris metabolism under varying light conditions requires further investigation.

Purpose of the Study:

• To develop an enhanced GSMM for Cordyceps militaris that incorporates light-dependent metabolic responses.
• To investigate the metabolic pathways involved in C. militaris adaptation to light using transcriptomic data.
• To improve the predictive capability of GSMMs for understanding fungal metabolism.

Main Methods:

• Integration of transcriptomic data with a genome-scale metabolic model (GSMM) of Cordyceps militaris.
• Application of the gene inactivity moderated by metabolism and expression (GIMME) framework.
• Development of the transcriptome-integrated GSMM (tiGSMM) model, iPS1474-tiGSMM.

Main Results:

• The iPS1474-tiGSMM model successfully simulated C. militaris metabolic responses under light exposure.
• The model demonstrated improved prediction of metabolic fluxes correlated with expressed genes in cordycepin and carotenoid biosynthesis.
• Reporter metabolite analysis identified central carbon, purine, and fatty acid metabolism as key processes for carotenoid production under light.

Conclusions:

• Transcriptome-integrated GSMMs provide a powerful approach to study light-mediated metabolic regulation in fungi.
• Key metabolic pathways involved in C. militaris acclimatization to light conditions were identified.
• This study offers insights for optimizing metabolite production in C. militaris by manipulating metabolic genes and fluxes.