Abstract: Shiraia bambusiccola is an important medicinal fungus in China. Hypocrellins with perylenequinone skeleton are main bioactive components of Shiraia bambusiccola, which are widely used in food, medicine, pesticide and other fields as natural photosensitizers. For example, "hypocrellin ointment" has already been used clinically. As a rare and vulnerable species, wild Shiraia bambusiccola resources are very limited. Due to the complex structure and chanllenge in chemical total synthesis of hypocrellins, it is urgent to find an effective strategy to rationally utilize its medicinal value while protecting the wild resources. In this study, a candidate gene cluster hpc was identified in Shiraia sp. cfcc 84681 based on careful bioinformatic analysis. A heterologous expression system for hpc gene cluster was successfully constructed and a mutant strain with high yield of hypocrellins was obtained, which mainly produced hypocrellin A and isohypocrellin A. The main ingredients in the mutant strain are consistent with that in the wild Shiraia bambusiccola. These results provide a new strategy to solve the shortage of wild Shiraia bambusiccola resources.