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/periodicalBook/Film/Article reviewScientific

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 languageEnglish
Article number107866
JournalBIOTECHNOLOGY ADVANCES
Volume54
DOIs
Publication statusPublished - 01 Jan 2022

Keywords

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

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