Genomics‐Driven Discovery of the Gliovirin Biosynthesis Gene Cluster in the Plant Beneficial Fungus Trichoderma Virens

Abstract

Gliovirin is a strong anti‐oomycete and a candidate anticancer compound. It is produced by “P” strains of the plant disease biocontrol fungus Trichoderma virens and is involved in biological control of certain plant pathogens. Even though the compound is known for more than three decades, neither the genes involved nor the biosynthetic pathway are known. We have sequenced the whole genome of a gliovirin producing strain of T. virens and discovered a novel gene cluster comprising of 22 genes. Disruption of the non‐ribosomal peptide synthetase eliminated biosynthesis of gliovirin. The gene cluster is very similar to a hitherto un‐described gene cluster of Aspergillus udagawae, a human pathogen. Our findings open‐up the possibility of strain improvement of T. virens for improved biocontrol of plant diseases through enhanced production of gliovirin. Research also can now be initiated on the role of this gene cluster in pathogenicity of the human pathogen A. udagawae.

The Viridin Biosynthesis Gene Cluster of Trichoderma virens and Its Conservancy in the Bat White‐Nose Fungus Pseudogymnoascus destructans

“…The scattering is due to poor assembly in this region as the intergenic regions are very large and contains AT‐rich repeats (indicating sub‐telomeric localization of this cluster). We were however successful in identifying the cluster in the recently published genome sequence of our strain (GVW) which was assembled using NGS . With the identification of the viridin gene cluster, it might now be possible to elucidate the entire biosynthetic pathway for this intriguing natural product.…”

“…Subsequent to the publication of the whole genome sequence of T. virens Gv29‐8, although we attempted to map these genes to the genome, we failed to identify the gene cluster, largely because of the scattering of the genes across contigs. Recently, we have sequenced another strain (GVW) of T. virens in our laboratory, and using this sequence (Acc. No.…”

Whole Genome Sequencing Reveals Major Deletions in the Genome of M7, a Gamma Ray-Induced Mutant of Trichoderma virens That Is Repressed in Conidiation, Secondary Metabolism, and Mycoparasitism

“…The viridin biosynthesis gene cluster comprises of 21 genes (Bansal et al, 2018), out of which, 16 genes were detected to be downregulated in M7. Similarly, the gliovirin biosynthetic gene cluster has 22 genes (Sherkhane et al, 2017), of which 16 genes were detected to be downregulated in M7. All the eight genes from the "vir" cluster, which are associated with volatile sesquiterpene compound production (Crutcher et al, 2013;Pachauri et al, 2019a), were downregulated in M7.…”

“…Whole genome of Gv29-8 and IMI304061 have been sequenced and analyzed, resulting in the identification of biosynthesis gene clusters for many unknown metabolites as well as for gliotoxin, gliovirin, viridin/viridiol, siderophores, and volatile sesquiterpenes (Kubicek et al, 2011;Crutcher et al, 2013;Sherkhane et al, 2017;Bansal et al, 2018;Mukherjee et al, 2018). Many hydrolytic enzymes and signal transduction proteins have been implicated to be involved in mycoparasitism of Trichoderma spp.…”

Non-lipopeptide fungi-derived peptide antibiotics developed since 2000

“…Structural modification of the DKP backbone is subsequently achieved by various tailoring enzymes including oxidoreductases, methyltransferases, prenyltransferases, cyclases and others (Wohlgemuth et al 2018). Table 1 shows fungi-derived DKPs for which biosynthases have been identified (Saruwatari et al 2014;Guo et al 2013;Yin et al 2009;Chankhamjon et al 2014;Maiya et al 2006Maiya et al , 2009Mundt et al 2012;Gerken and Walsh 2013;Oide et al 2006;Wilhite et al 2001;Wohlgemuth et al 2017Wohlgemuth et al , 2018Lazos et al 2010;Lim et al 2014;Gardiner and Howlett 2005;Sherkhane et al 2017;Chu et al 2010;García-Estrada et al 2011;Ali et al2013;Gardiner et al 2004;Dopstadt et al 2016;Wang et al 2017c;Quezada et al 2017). Peptides lacking special functional groups in the short oligopeptide nucleus are herein referred to as typical peptides.…”