Molecular Genetics of Secondary Chemistry in Metarhizium Fungi

As with many microbes, entomopathogenic fungi from the genus Metarhizium produce a plethora of small molecule metabolites, often referred to as secondary metabolites. Although these intriguing compounds are a conspicuous feature of the biology of the producing fungi, their roles in pathogenicity and other interactions with their hosts and competing microbes are still not well understood. In this review, secondary metabolites that have been isolated from Metarhizium are cataloged along with the history of their discovery and structural elucidation and the salient biological activities attributed to them. Newly available genome sequences revealed an abundance of biosynthetic pathways and a capacity for producing SMs by Metarhizium species that far exceeds the known chemistry. Secondary metabolism genes identified in nine sequenced Metarhizium species are analyzed in detail and classified into distinct families based on orthology, phylogenetic analysis, and conservation of the gene organization around them. This analysis led to the identification of seven hybrid polyketide/nonribosomal peptide synthetases (M-HPNs), two inverted hybrid nonribosomal peptide/polyketide synthetases (M-IHs), 27 nonribosomal peptide synthetases (M-NRPSs), 14 nonribosomal peptide synthetase-like (M-NPL) pathways, 32 polyketide synthases, and 44 terpene biosynthetic genes having a nonuniform distribution and largely following established phylogenetic relationships within the genus Metarhzium. This systematization also identified candidate pathways for known Metarhizium chemistries and predicted the presence of unknown natural products for this genus by drawing connections between these pathways and natural products known to be produced by other fungi.