Biotechnological production and potential applications of hypocrellins

Hypocrellins (HYPs), a kind of natural perylenequinones (PQs) with an oxidized pentacyclic core, are important natural compounds initially extracted from the stromata of Hypocrella bambusae and Shiraia bambusicola. They have been widely concerned for their use as anti-microbial, anti-cancers, and anti-viral photodynamic therapy agents in recent years. Considering the restrictions of natural stromal resources, submerged fermentation with Shiraia spp. has been viewed as a promising alternative biotechnology for HYP production, and great efforts have been made to improve HYP production over the past decade. This article reviews recent publications about the mycelium fermentation production of HYPs, and their bioactivities and potential applications, and especially summarizes the progresses toward manipulation of fermentation conditions. Also, their chemical structure and analytic methods are outlined. Herein, it is worth mentioning that the gene arrangement in HYP gene cluster is revised; previous unknown genes in HYP and CTB gene clusters with correct function annotation are deciphered; the homologous sequences of HYP, CTB, and elc are systematically aligned, and especially the biosynthetic pathway of HYPs is full-scale proposed. KEY POINTS: • The mycelial fermentation process and metabolic regulation of hypocrellins are reviewed. • The bioactivities and potential applications of hypocrellins are summarized. • The biosynthesis pathway and regulatory mechanisms of hypocrellins are outlined.