No Cover Image

Journal article 33 views 8 downloads

Discovery of a fungal Tc toxin complex and functional mycoserpin through a novel two-by-two comparative genomics approach

Zack Saud, Yujuan Luo, Martyn J Wood, Ian Boostrom, Bruce J MacLachlan, Richard J Stanton, Chengshu Wang, Tariq Butt Orcid Logo

Frontiers in Cellular and Infection Microbiology, Volume: 16, Start page: 1800461

Swansea University Authors: Zack Saud, Tariq Butt Orcid Logo

  • 72098.VOR.pdf

    PDF | Version of Record

    © 2026 Saud, Luo, Wood, Boostrom, MacLachlan, Stanton, Wang and Butt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

    Download (2.55MB)

Check full text

DOI (Published version): 10.3389/fcimb.2026.1800461

Abstract

Introduction: Fungi have been a rich source of pharmaceuticals such as antibiotics, immunosuppressants, and cholesterol-lowering drugs; however, their therapeutic potential remains largely untapped due to difficulties in culturing and elucidating the genetic basis of beneficial traits. Fungi contain...

Full description

Published in: Frontiers in Cellular and Infection Microbiology
ISSN: 2235-2988
Published: Frontiers Media SA 2026
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa72098
Abstract: Introduction: Fungi have been a rich source of pharmaceuticals such as antibiotics, immunosuppressants, and cholesterol-lowering drugs; however, their therapeutic potential remains largely untapped due to difficulties in culturing and elucidating the genetic basis of beneficial traits. Fungi contain ‘cryptic’ genes that are expressed under certain, and often obscure, growth conditions and can produce complex compounds that are difficult to synthesize economically. Developments in genome sequencing and DNA-synthesis technologies offer new opportunities to produce such compounds using biotechnological techniques, however, accurately identifying useful and novel genes, a prerequisite for such approaches, remains challenging.Methods: We present a novel ‘two-by-two’ comparative genomics pipeline for comprehensive gene analysis of selected fungal groups, enabling more confident identification of unique genes across the analyzed species. The approach compares gene sets from two strains of the same species with those from two strains of different species or families within a fungal order. Self-clustering orthologs that are unique to strains from the same species provide higher confidence in identifying species-specific proteins and help reduce noise from low-quality genome assemblies and gene prediction errors.Results: We validated our method in a well-studied fungal group, correctly identifying known species-specific genes and gene clusters, and discovering a novel functional myco-serpin and a fungal Tc toxin complex in Metarhizium.Discussion: Elucidating the genes underlying beneficial traits in fungi presents significant challenges, largely due to the unique and relatively complex aspects of their lifestyles. The two-by-two approach shows broad potential for fungal genome mining and bioprospecting, demonstrated by our discovery of the first fungal Tc toxin complex and a functional myco-serpin in Metarhizium (Hypocreales), and is applicable to other fungal orders such as Eurotiales and Xylariales. Furthermore, the two-by-two approach can be adapted to other organisms with genome architectures similar to fungi.
Keywords: bioinformatics, biosynthetic gene cluster, comparative genomics, fungi, hypocreales, infection, serpin, Tc toxin
College: Faculty of Science and Engineering
Funders: ZS was supported by a Wellcome Trust grant (226615/Z/22/Z) awarded to RJS. YL was supported by grants from the National Natural Science Foundation of China (No. 32021001 and 32230087) awarded to CW.
Start Page: 1800461

Similar Items