Biosynthesis and molecular regulatory mechanisms of camptothecin in fungi

Abstract

Abstract Camptothecin (CPT) is one of the common chemotherapies for tumors, for its superior affinity for inhibiting the Topoisomerase I activity via stabilizing the enzyme–DNA ternary complex, thus precluding the relaxation of DNA in the frequently replicated cells. CPT was initially derived from the bark of chinese Happy tree plants “ Camptotheca acuminata ”. However, availability of the CPT and their derivatives is the main challenge that halts the further implementation of this compound. The fungal biosynthetic potency of CPT raises the prospective for the production of CPT, due to their short lifespan and feasibility of bulk biomass bioprocessing, nevertheless, weakening of the CPT productivity with the fungal storage consecutive subculturing are the challenge. So, this review was to unravel the biosynthetic potency of CPT and their molecular regulatory processes to sustain the CPT productivity by fungi by exploring the rate-limiting enzymes, epigenetic regulators and transcriptional factors of CPT biosynthesis. As well as, to explore the expression of CPT biosynthetic gene clusters regarding to chromatin remodeling, microbial-microbial crosstalk, in relation to deciphering the CPT biosynthesis gene cluster by fungi.