Developing fungal heterologous expression platforms to explore and improve the production of natural products from fungal biodiversity

Xiangfeng Meng; Yu Fang; Mingyang Ding; Yanyu Zhang; Kaili Jia; Zhongye Li; Jérôme Collemare; Weifeng Liu

doi:10.1016/j.biotechadv.2021.107866

Developing fungal heterologous expression platforms to explore and improve the production of natural products from fungal biodiversity

Xiangfeng Meng, Yu Fang, Mingyang Ding, Yanyu Zhang, Kaili Jia, Zhongye Li, Jérôme Collemare^*, Weifeng Liu

^*Corresponding author for this work

Research output: Contribution to journal/periodical › Book/Film/Article review › Scientific

18 Citations (Scopus)

Abstract

Natural products from fungi represent an important source of biologically active metabolites notably for therapeutic agent development. Genome sequencing revealed that the number of biosynthetic gene clusters (BGCs) in fungi is much larger than expected. Unfortunately, most of them are silent or barely expressed under laboratory culture conditions. Moreover, many fungi in nature are uncultivable or cannot be genetically manipulated, restricting the extraction and identification of bioactive metabolites from these species. Rapid exploration of the tremendous number of cryptic fungal BGCs necessitates the development of heterologous expression platforms, which will facilitate the efficient production of natural products in fungal cell factories. Host selection, BGC assembly methods, promoters used for heterologous gene expression, metabolic engineering strategies and compartmentalization of biosynthetic pathways are key aspects for consideration to develop such a microbial platform. In the present review, we summarize current progress on the above challenges to promote research effort in the relevant fields.

Original language	English
Article number	107866
Journal	BIOTECHNOLOGY ADVANCES
Volume	54
DOIs	https://doi.org/10.1016/j.biotechadv.2021.107866
Publication status	Published - 01 Jan 2022

Keywords

Biosynthetic gene cluster
Compartmentalization
Genomics
Metabolic engineering
Microbial chassis
Promoter
Synthetic biology

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10.1016/j.biotechadv.2021.107866

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title = "Developing fungal heterologous expression platforms to explore and improve the production of natural products from fungal biodiversity",

abstract = "Natural products from fungi represent an important source of biologically active metabolites notably for therapeutic agent development. Genome sequencing revealed that the number of biosynthetic gene clusters (BGCs) in fungi is much larger than expected. Unfortunately, most of them are silent or barely expressed under laboratory culture conditions. Moreover, many fungi in nature are uncultivable or cannot be genetically manipulated, restricting the extraction and identification of bioactive metabolites from these species. Rapid exploration of the tremendous number of cryptic fungal BGCs necessitates the development of heterologous expression platforms, which will facilitate the efficient production of natural products in fungal cell factories. Host selection, BGC assembly methods, promoters used for heterologous gene expression, metabolic engineering strategies and compartmentalization of biosynthetic pathways are key aspects for consideration to develop such a microbial platform. In the present review, we summarize current progress on the above challenges to promote research effort in the relevant fields.",

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author = "Xiangfeng Meng and Yu Fang and Mingyang Ding and Yanyu Zhang and Kaili Jia and Zhongye Li and J{\'e}r{\^o}me Collemare and Weifeng Liu",

note = "Funding Information: This work was supported by National Key R&D Program of China (No. 2019YFA0905700 ), National Natural Science Foundation of China ( 31800047 , 31970071 ), Major Basic Research of Shandong Provincial Natural Science Foundation ( ZR2019ZD19 ), Young Scholars Program of Shandong University . Publisher Copyright: {\textcopyright} 2021 The Authors",

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doi = "10.1016/j.biotechadv.2021.107866",

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AU - Meng, Xiangfeng

AU - Fang, Yu

AU - Ding, Mingyang

AU - Zhang, Yanyu

AU - Jia, Kaili

AU - Li, Zhongye

AU - Collemare, Jérôme

AU - Liu, Weifeng

N1 - Funding Information: This work was supported by National Key R&D Program of China (No. 2019YFA0905700 ), National Natural Science Foundation of China ( 31800047 , 31970071 ), Major Basic Research of Shandong Provincial Natural Science Foundation ( ZR2019ZD19 ), Young Scholars Program of Shandong University . Publisher Copyright: © 2021 The Authors

PY - 2022/1/1

Y1 - 2022/1/1

N2 - Natural products from fungi represent an important source of biologically active metabolites notably for therapeutic agent development. Genome sequencing revealed that the number of biosynthetic gene clusters (BGCs) in fungi is much larger than expected. Unfortunately, most of them are silent or barely expressed under laboratory culture conditions. Moreover, many fungi in nature are uncultivable or cannot be genetically manipulated, restricting the extraction and identification of bioactive metabolites from these species. Rapid exploration of the tremendous number of cryptic fungal BGCs necessitates the development of heterologous expression platforms, which will facilitate the efficient production of natural products in fungal cell factories. Host selection, BGC assembly methods, promoters used for heterologous gene expression, metabolic engineering strategies and compartmentalization of biosynthetic pathways are key aspects for consideration to develop such a microbial platform. In the present review, we summarize current progress on the above challenges to promote research effort in the relevant fields.

AB - Natural products from fungi represent an important source of biologically active metabolites notably for therapeutic agent development. Genome sequencing revealed that the number of biosynthetic gene clusters (BGCs) in fungi is much larger than expected. Unfortunately, most of them are silent or barely expressed under laboratory culture conditions. Moreover, many fungi in nature are uncultivable or cannot be genetically manipulated, restricting the extraction and identification of bioactive metabolites from these species. Rapid exploration of the tremendous number of cryptic fungal BGCs necessitates the development of heterologous expression platforms, which will facilitate the efficient production of natural products in fungal cell factories. Host selection, BGC assembly methods, promoters used for heterologous gene expression, metabolic engineering strategies and compartmentalization of biosynthetic pathways are key aspects for consideration to develop such a microbial platform. In the present review, we summarize current progress on the above challenges to promote research effort in the relevant fields.

KW - Biosynthetic gene cluster

KW - Compartmentalization

KW - Genomics

KW - Metabolic engineering

KW - Microbial chassis

KW - Promoter

KW - Synthetic biology

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JO - BIOTECHNOLOGY ADVANCES

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Developing fungal heterologous expression platforms to explore and improve the production of natural products from fungal biodiversity

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