Sagita Rosa, Quax Wim J, Haslinger Kristina
Groningen Institute of Pharmacy, Chemical and Pharmaceutical Biology, University of Groningen, Groningen, Netherlands.
Front Bioeng Biotechnol. 2021 Mar 15;9:649906. doi: 10.3389/fbioe.2021.649906. eCollection 2021.
The bioprospecting of secondary metabolites from endophytic fungi received great attention in the 1990s and 2000s, when the controversy around taxol production from 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.
20世纪90年代和21世纪初，从内生真菌中进行次生代谢产物的生物勘探备受关注，当时围绕红豆杉内生菌生产紫杉醇的争议正处于白热化阶段。从那时起，数百篇报告描述了从内生真菌中分离和鉴定推定的次生代谢产物。然而，只有极少数研究也报道了这些表型观察结果的遗传基础。随着测序成本的降低和样本周转速度的加快，基于遗传学和基因组学的方法已成为研究来自广泛生物体的天然产物的综合方法，特别是用于阐明潜在的生物合成途径。然而，在真菌内生菌生物学领域，阐明生物合成途径仍然是一项重大挑战。作为一类研究相对较少的微生物群体，即使考虑到最近对更多真菌基因组进行测序的努力，如联合基因组研究所（JGI）的1000真菌基因组计划，从内生真菌中进行酶和途径生物勘探的基础仍然相当薄弱。在本综述中，我们想通过生物勘探的视角，讨论目前用于将表型和基因型关联起来以阐明内生真菌次生代谢产物生物合成途径的方法和工具。本综述将指出已报道的成功和不足之处，并讨论内生真菌采样、遗传学和基因组学的未来方向。鉴定从内生真菌中分离出的众多次生代谢产物的负责生物合成基因，为探索生产菌株的遗传潜力以发现新型次生代谢产物并通过代谢工程提高次生代谢产物产量开辟了机会，从而产生新型且更经济实惠的药物和食品添加剂。
