Recent developments of tools for genome and metabolome studies in basidiomycete fungi and their application to natural product research

Abstract

Basidiomycota are a large and diverse phylum of fungi. They can make bioactive metabolites that are used or have inspired the synthesis of antibiotics and agrochemicals. Terpenoids are the most abundant class of natural products encountered in this taxon. Other natural product classes have been described, including polyketides, peptides, and indole alkaloids. The discovery and study of natural products made by basidiomycete fungi has so far been hampered by several factors, which include their slow growth and complex genome architecture. Recent developments of tools for genome and metabolome studies are allowing researchers to more easily tackle the secondary metabolome of basidiomycete fungi. Inexpensive long-read whole-genome sequencing enables the assembly of high-quality genomes, improving the scaffold upon which natural product gene clusters can be predicted. CRISPR/Cas9-based engineering of basidiomycete fungi has been described and will have an important role in linking natural products to their genetic determinants. Platforms for the heterologous expression of basidiomycete genes and gene clusters have been developed, enabling natural product biosynthesis studies. Molecular network analyses and publicly available natural product databases facilitate data dereplication and natural product characterisation. These technological advances combined are prompting a revived interest in natural product discovery from basidiomycete fungi.This article has an associated Future Leader to Watch interview with the first author of the paper.

Microbial hosts for metabolic engineering of lignin bioconversion to renewable chemicals

“…White-rot basidiomycete fungi are among the most powerful and efficient lignin degrading microorganisms known [50]. The development of genetic engineering tools for basidiomycetes -white-rot fungi being no exception -has traditionally been hampered by their long life-cycle, complex gene architecture, low efficiency of DNA fragment insertion into the chromosomes and protoplast production from spores [51,52]. Nevertheless, metabolic engineering efforts of white-rot fungi for lignin degradation have been undertaken giving promising results.…”

Naturally Occurring Terpenes: A Promising Class of Organic Molecules to Address Influenza Pandemics

“…Bioactive compounds are organic molecules with normally small molecular weight that can be produced by both Ascomycetes and Basidiomycetes. Literature reports on fungal antiviral sources reveal that most known bioactive molecules have been isolated from Ascomycetes and Basidiomycetes, providing insights into the competence of those two phyla as producers of therapeutic compounds [ 45 – 48 ]. The studies indicated also that the biosynthetic gene clusters of the bioactive metabolites’ dominance are generally lower in number in basidiomycetes compared to the ascomycetes.…”

“…H1N1and HSV-1 HSV-I Antiviral activity [43,44] two phyla as producers of therapeutic compounds [45][46][47][48].…”

Applications of CRISPR/Cas Gene-Editing Technology in Fungi

“…Macrofungi are multicellular eukaryotes; most are binucleate or multinucleated cells. The low e ciency of obtaining homozygous mutations makes it di cult to achieve the speci c modi cation of target genes and multigene knockout or gene insertion mutations, thereby limiting basic research focused on macrofungi (Alberti et al 2020)…”