Secondary metabolites from hypocrealean entomopathogenic fungi: genomics as a tool to elucidate the encoded parvome.

Covering: 2014 up to the third quarter of 2019 Hypocrealean entomopathogenic fungi (HEF) produce a large variety of secondary metabolites (SMs) that are prominent virulence factors or mediate various interactions in the native niches of these organisms. Many of these SMs show insecticidal, immune system modulatory, antimicrobial, cytotoxic and other bioactivities of clinical or agricultural significance. Recent advances in whole genome sequencing technologies and bioinformatics have revealed many biosynthetic gene clusters (BGCs) potentially involved in SM production in HEF. Some of these BGCs are now well characterized, with the structures of the cognate product congeners elucidated, and the proposed biosynthetic functions of key enzymes validated. However, the vast majority of HEF BGCs are still not linked to SM products ("orphan" BGCs), including many clusters that are not expressed (silent) under routine laboratory conditions. Thus, investigations into the encoded parvome (the secondary metabolome predicted from the genome) of HEF allows the discovery of BGCs for known SMs; uncovers novel metabolites based on the BGCs; and catalogues the predicted SM biosynthetic potential of these fungi. Herein, we summarize new developments of the field, and survey the polyketide, nonribosomal peptide, terpenoid and hybrid SM BGCs encoded in the currently available 40 HEF genome sequences. Studying the encoded parvome of HEF will increase our understanding of the multifaceted roles that SMs play in biotic and abiotic interactions and will also reveal biologically active SMs that can be exploited for the discovery of human and veterinary drugs or crop protection agents.