Biotechnological strategies for production of camptothecin from fungal and bacterial endophytes

Abstract

The horrifying impact of emergence of cancer as an endemic disease worldwide associated with accelerated mortality rate caused significant boost in anticancer drug discovery. The most successful broad spectrum anti-neoplastic monoterpene indole alkaloid camptothecin (CPT) is the product of such natural product based therapeutic approach. This promising anticancer compound, currently approved against cancer, was first isolated from Camptotheca acuminata of Nyssaceae family and was reported as a potent inhibitor of eukaryotic topoisomerase I. Despite its continuous success under clinical studies, low accumulation, slow growth and over-exploitation of Camptotheca acuminata, high extraction cost, complex nature of total, semi and chemical synthesis has failed to meet the industrial demand. As an alternative bio-prospecting route, fermentation of endophytic microbial culture and co-culture of CPT producing plant cell suspension with endophytes have evolved. Endophytes are reported for their contribution in plant growth, disease resistance, stress tolerance and agricultural productivity which may have contributed to scale up the CPT production. This review sums up the current trend in endophytic microbes-based CPT biosynthesis and biotechnological strategies for optimization of CPT yield. Moreover, interaction of endophytic fungi with different host plants under experimental variables, their mode of elicitation, possibility of microbial strain improvement via application of biotechnological strategies and respective lacunas are also being elucidated.