Trichoderma: A Treasure House of Structurally Diverse Secondary Metabolites With Medicinal Importance

Abstract

Fungi play an irreplaceable role in drug discovery in the course of human history, as they possess unique abilities to synthesize diverse specialized metabolites with significant medicinal potential. Trichoderma are well-studied filamentous fungi generally observed in nature, which are widely marketed as biocontrol agents. The secondary metabolites produced by Trichoderma have gained extensive attention since they possess attractive chemical structures with remarkable biological activities. A large number of metabolites have been isolated from Trichoderma species in recent years. A previous review by Reino et al. summarized 186 compounds isolated from Trichoderma as well as their biological activities up to 2008. To update the relevant list of reviews of secondary metabolites produced from Trichoderma sp., we provide a comprehensive overview in regard to the newly described metabolites of Trichoderma from the beginning of 2009 to the end of 2020, with emphasis on their chemistry and various bioactivities. A total of 203 compounds with considerable bioactivities are included in this review, which is worth expecting for the discovery of new drug leads and agrochemicals in the foreseeable future. Moreover, new strategies for discovering secondary metabolites of Trichoderma in recent years are also discussed herein.

Genetic Evidence in Favor of a Polyketide Origin of Acremeremophilanes, the Fungal “Sesquiterpene” Metabolites

“…Plant beneficial effects of these microbes have been attributed to their ability to kill/inhibit other fungi, to boost plant immunity, and to the production of a large array of secondary (specialized) metabolites ( 5 – 10 ). About 400 small molecule secondary metabolites (mainly nonribosomal peptides, polyketides, and terpenes) have been reported from Trichoderma spp., in addition to more than 1000 peptaibols ( 5 , 7 ). Trichoderma virens is one of the most researched species for genetics, genomics, and development of commercial formulations ( 11 – 13 ).…”

Designing synthetic consortia of Trichoderma strains that improve antagonistic activities against pathogens and cucumber seedling growth

“…Trichoderma has a remarkable diverse metabolism capable of catabolizing a wide variety of substrates as well as producing a wide variety of secondary metabolites(SMs), of which those most studied are peptaibols, polyketides, pyrones, terpenes and diketopiperazine-like compounds, etc. Many of these compounds are closely involved in biological control and plant growth promotion [ 11 , 12 ]. Genome sequencing of Trichoderma strains in monoculture shows that most of the biosynthetic gene clusters related to secondary metabolites are hidden (transcriptional silencing) or expressed at a very low level under general laboratory conditions, suggesting that these silent metabolic pathways need to be stimulated in some way before they are expressed to produce new metabolites or adequate amounts of metabolites with varied functions.…”

Use of CRISPR‐Cas tools to engineer Trichoderma species

“…In recent years, a range of Trichoderma applications has undergone considerable expansion, facilitated by rapid ongoing developments in the field of biotechnology (Benitez et al, 2004 ; Bischof et al, 2016 ; TariqJaveed et al, 2021 ; Xie et al, 2021 ; Zhang et al, 2021 ). Notable in this regard has been the advances made in genetic modification and the generation of massive amounts of genomic data for this genus, including T. reesei (Martinez et al, 2008 ), T. atroviride (Kubicek et al, 2011 ), T. virens (Kubicek et al, 2011 ), T. longibrachiatum (Kubicek et al, 2011 ), T. harzianum (Steindorff et al, 2014 ), and T. asperellum (Druzhinina et al, 2018 ; Kubicek et al, 2019 ; Li, Lin et al, 2021 ; Li, Liu et al, 2021 ).…”