Trichoderma reesei Set2 modulates sorbicillinoid biosynthesis via regulating the expression of transcription factor Ypr1

Abstract:

[Objective] Sorbicillinoids are important natural active compounds synthesized by Trichoderma reesei and exhibit various biological activities, such as antineoplastic, antioxidative, and antiviral properties. In this study, we aimed to clarify the biological functions and regulatory mechanisms of TrSet2 during sorbicillinoid biosynthesis in T. reesei. [Methods] Weidentified the gene encoding TrSet2 in T. reesei using bioinformatic analysis, and investigated its functions in sorbicillinoid biosynthesis by knockouting and overexpressing Trset2 gene. In addition, the transcription activator Ypr1 was overexpressed in Trset2 knockout strain to elucidate the regulatory mechanism between TrSet2 and Ypr1. [Results] Knockout of Trset2 led to the strain's inability to synthesize sorbicillinoids. Conversely, overexpression of Trset2 resulted in a significant increase in sorbicillinoid secretion. Further studies showed that overexpression of Ypr1 in Trset2 knockout strain restored sorbicillinoid production. [Conclusion] TrSet2 positively regulated the sorbicillinoid biosynthesis via controlling the expression of Ypr1. Our results facilitated the control of sorbicillinoid secretion during the fermentation of T. reesei and the development of cell factories for high-level synthesis of sorbicillinoids based on the regulatory mechanism.