Molecular genetics of secondary chemistry in Metarhizium fungi

Authors: DONZELLI, BRUNO GUILIANO - Cornell University; Krasnoff, Stuart

Submitted to: Advances in Genetics
Publication Type: Review Article
Publication Acceptance Date: 2/9/2016
Publication Date: 4/28/2016
Citation: Donzelli, B.G., Krasnoff, S. 2016. Molecular genetics of secondary chemistry in Metarhizium fungi. Advances in Genetics. 94:365-436.

Interpretive Summary: The fungal genus Metarhizium comprises approximately 30 species, many of which are widespread geographically and infect a wide range of insect species including injurious agricultural pests. Thus, this group of fungi is important because of its potential as a natural biocontrol agent of insects. Several species of Metarhizium have been commercialized as safe pesticides and are now important components of integrated pest management programs. Metarhizium fungi produce an exceptionally large number of unique small molecule metabolites, aka secondary metabolites. In light of the key role played by these molecules in pathogenic processes, we explored the genomes of nine sequenced Metarhizium species to identify and compare the genes that control secondary metabolite production. This information will help in the future analyses of these genes and in the development of methods to inactivate specific secondary metabolites. This work also contributes to our understanding of how these fungi successfully infect and kill insects and, ultimately, how they impact the success of these fungi as biocontrol agents.

Technical Abstract: 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, SMs 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 non-uniform 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.