The Biosynthetic Gene Cluster of Mushroom-Derived Antrocin Encodes Two Dual-Functional Haloacid Dehalogenase-like Terpene Cyclases.

(-)-Antrocin (1), produced by the medicinal mushroom Antrodia cinnamomea, is a potent antiproliferative compound. The biosynthetic gene cluster of 1 was identified, and the pathway was characterized by heterologous expression. We characterized a haloacid dehalogenase-like terpene cyclase AncC that biosynthesizes the drimane-type sesquiterpene (+)-albicanol (2) from farnesyl pyrophosphate (FPP). Biochemical characterization of AncC, including kinetic studies and mutagenesis, demonstrated the functions of two domains: a terpene cyclase (TC) and a pyrophosphatase (PPase). The TC domain first cyclizes FPP to albicanyl pyrophosphate, and the PPase domain then removes the pyrophosphate to form 2. Intriguingly, AncA (94 % sequence identity to AncC), in the same gene cluster, converts FPP into (R)-trans-γ-monocyclofarnesol instead of 2. Notably, Y283/F375 in the TC domain of AncA serve as a gatekeeper in controlling the formation of a cyclofarnesoid rather than a drimane-type scaffold.

Biosynthesis of bioactive natural products from Basidiomycota.

The Basidiomycota, also called club fungi, comprise a diverse group of fungi. Basidiomycota are strongly related to ecosystem functioning along with human life. These fungi display a wide range of bioactivities, and some are known to produce of deadly toxins or hallucinogens. Some Basidiomycota have be used as medicinal mushrooms for thousands of years. Recently, the biosyntheses of several classes of natural products from Basidiomycota have been reported. Here, we review recent studies on the biosynthetic pathways and enzymes of bioactive natural products from Basidiomycota fungi, with a focus on terpenoids, alkaloids, ribosomally synthesized and post-translationally modified peptides (RiPPs), and polyketides.