Metformin regulates cellulase production in Trichoderma reesei via calcium signaling and mitochondrial function.

Background: Trichoderma reesei is renowned for its cellulase-producing ability and is used for biofuel production from lignocellulose. In plants and fungi, cellulase production is induced by cellulose and suppressed by glucose; however, whether metformin can enhance cellulase production and mitochondrial function in T. reesei remains unclear. Metformin reduces blood glucose levels by inhibiting hepatic gluconeogenesis; therefore, it is worth investigating whether metformin transmission modulates cellulase biosynthesis in T. reesei.

Results: Metformin increased cellulase production and the transcription of cellulase-related genes. It also enhanced the concentrations of Ca²⁺ in the cytosol and mitochondria and regulated the transcription levels of cellulase-related genes by modulating calcium homeostasis in T. reesei QM6a. In addition, metformin was identified as an antioxidant that can enhance cellulase activity by reducing reactive oxygen species (ROS). Our results demonstrated that metformin influences the state of mitochondria by enhancing mitochondrial activity and membrane potential to promote cellulase production.

Conclusion: Collectively, these results indicate that metformin enhances cellulase production, scavenges ROS, and protects mitochondrial activity in T. reesei.