Abstract
The bioprospecting of secondary metabolites from endophytic fungi received great attention in the 1990s and 2000s, when the controversy around taxol production from Taxus spp. endophytes was at its height. Since then, hundreds of reports have described the isolation and characterization of putative secondary metabolites from endophytic fungi. However, only very few studies also report the genetic basis for these phenotypic observations. With low sequencing cost and fast sample turnaround, genetics- and genomics-based approaches have risen to become comprehensive approaches to study natural products from a wide-range of organisms, especially to elucidate underlying biosynthetic pathways. However, in the field of fungal endophyte biology, elucidation of biosynthetic pathways is still a major challenge. As a relatively poorly investigated group of microorganisms, even in the light of recent efforts to sequence more fungal genomes, such as the 1000 Fungal Genomes Project at the Joint Genome Institute (JGI), the basis for bioprospecting of enzymes and pathways from endophytic fungi is still rather slim. In this review we want to discuss the current approaches and tools used to associate phenotype and genotype to elucidate biosynthetic pathways of secondary metabolites in endophytic fungi through the lens of bioprospecting. This review will point out the reported successes and shortcomings, and discuss future directions in sampling, and genetics and genomics of endophytic fungi. Identifying responsible biosynthetic genes for the numerous secondary metabolites isolated from endophytic fungi opens the opportunity to explore the genetic potential of producer strains to discover novel secondary metabolites and enhance secondary metabolite production by metabolic engineering resulting in novel and more affordable medicines and food additives.
Highlights
Endophyte is an all-encompassing term that refers to organisms which, within a certain period of their life, colonize the interior organs of their plant hosts (Box 1)
As reviewed we expect that some of these problems will be overcome with the availability of more functional genomics studies in fungi and especially endophytic fungi
The real challenge appears to be the discovery of the underlying biosynthetic pathways that would allow the rational engineering, or refactoring of these pathways for industrial purposes
Summary
Endophyte is an all-encompassing term that refers to organisms which, within a certain period of their life, colonize the interior organs of their plant hosts (Box 1). Considering that the nature of many pathways in fungi is silent or attenuated under unfavorable experimental conditions (Keller, 2019), the qualitative and quantitative profiles of metabolites in organisms exposed to different growth conditions provide a holistic overview of their biochemical status and allows for an exploitation of their natural biogenetic capability This approach is known under the acronym OSMAC, One Strain-Many Compounds (Bode et al, 2002), and has led to several interesting secondary metabolite discoveries in a wide range of organisms, including endophytic fungi (Pan et al, 2019). Other studies rely more to the bioassay-guided approach with consecutive fractionations of the fungal extract to the smallest fraction containing a single active substance with the target bioactivity Based on this strategy, a diketopiperazine cyclo (L-Pro-L-Phe) (7), with antibacterial activity against Salmonella enterica was discovered for the first time in the endophytic fungus Paraphaeosphaeria sporulosa (Carrieri et al, 2020).
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