Anticancer fungal natural products: Mechanisms of action and biosynthesis

Many fungal metabolites show promising anticancer properties both in vitro and in animal models, and some synthetic analogs of those metabolites have progressed into clinical trials. However, currently, there are still no fungi-derived agents approved as anticancer drugs. Two potential reasons could be envisioned: 1) lacking a clear understanding of their anticancer mechanism of action, 2) unable to supply enough materials to support the preclinical and clinic developments. In this review, we will summarize recent efforts on elucidating the anticancer mechanisms and biosynthetic pathways of several promising anticancer fungal natural products. • The biosynthesis and mode of action of anticancer fungal natural products are summarized. • Biosynthesis is mainly invested by the combination of gene inactivation of producing strains, and heterologous expression. • Combinatorial biosynthesis is still rare compared to that of bacterial natural products. • Most of those natural products bind to co-factor binding sites. • Covalent inhibition with reactive motives are frequently observed.