Expression of fungal biosynthetic gene clusters in S. cerevisiae for natural product discovery

Fungi are well known for production of antibiotics and other bioactive secondary metabolites, that can be served as pharmaceuticals, therapeutic agents and industrially useful compounds. However, compared with the characterization of prokaryotic biosynthetic gene clusters (BGCs), less attention has...

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Main Authors: Zihe Liu, Zhenquan Lin, Jens Nielsen
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2021-03-01
Series:Synthetic and Systems Biotechnology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405805X2100003X
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author Zihe Liu
Zhenquan Lin
Jens Nielsen
author_facet Zihe Liu
Zhenquan Lin
Jens Nielsen
author_sort Zihe Liu
collection DOAJ
description Fungi are well known for production of antibiotics and other bioactive secondary metabolites, that can be served as pharmaceuticals, therapeutic agents and industrially useful compounds. However, compared with the characterization of prokaryotic biosynthetic gene clusters (BGCs), less attention has been paid to evaluate fungal BGCs. This is partially because heterologous expression of eukaryotic gene constructs often requires replacement of original promoters and terminators, as well as removal of intron sequences, and this substantially slow down the workflow in natural product discovery. It is therefore of interest to investigate the possibility and effectiveness of heterologous expression and library screening of intact BGCs without refactoring in industrial friendly microbial cell factories, such as the yeast Saccharomyces cerevisiae. Here, we discuss the importance of developing new research directions on library screening of fungal BGCs in yeast without refactoring, followed by outlooking prominent opportunities and challenges for future advancement.
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spelling doaj.art-4836c1f1735a4c2a99dac9a0c68ffc342024-04-16T12:01:36ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2021-03-01612022Expression of fungal biosynthetic gene clusters in S. cerevisiae for natural product discoveryZihe Liu0Zhenquan Lin1Jens Nielsen2College of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, 100029, Beijing, ChinaCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, 100029, Beijing, ChinaCollege of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, 100029, Beijing, China; Department of Biology and Biological Engineering, Chalmers University of Technology, SE412 96, Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK2800, Lyngby, Denmark; BioInnovation Institute, Ole Maaløes Vej 3, DK2200, Copenhagen N, Denmark; Corresponding author. College of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, 100029, Beijing, China.Fungi are well known for production of antibiotics and other bioactive secondary metabolites, that can be served as pharmaceuticals, therapeutic agents and industrially useful compounds. However, compared with the characterization of prokaryotic biosynthetic gene clusters (BGCs), less attention has been paid to evaluate fungal BGCs. This is partially because heterologous expression of eukaryotic gene constructs often requires replacement of original promoters and terminators, as well as removal of intron sequences, and this substantially slow down the workflow in natural product discovery. It is therefore of interest to investigate the possibility and effectiveness of heterologous expression and library screening of intact BGCs without refactoring in industrial friendly microbial cell factories, such as the yeast Saccharomyces cerevisiae. Here, we discuss the importance of developing new research directions on library screening of fungal BGCs in yeast without refactoring, followed by outlooking prominent opportunities and challenges for future advancement.http://www.sciencedirect.com/science/article/pii/S2405805X2100003XNatural product discoveryCross-species engineeringSpliceosomeHigh-throughput BGC cloningSynthetic biologyYeast
spellingShingle Zihe Liu
Zhenquan Lin
Jens Nielsen
Expression of fungal biosynthetic gene clusters in S. cerevisiae for natural product discovery
Synthetic and Systems Biotechnology
Natural product discovery
Cross-species engineering
Spliceosome
High-throughput BGC cloning
Synthetic biology
Yeast
title Expression of fungal biosynthetic gene clusters in S. cerevisiae for natural product discovery
title_full Expression of fungal biosynthetic gene clusters in S. cerevisiae for natural product discovery
title_fullStr Expression of fungal biosynthetic gene clusters in S. cerevisiae for natural product discovery
title_full_unstemmed Expression of fungal biosynthetic gene clusters in S. cerevisiae for natural product discovery
title_short Expression of fungal biosynthetic gene clusters in S. cerevisiae for natural product discovery
title_sort expression of fungal biosynthetic gene clusters in s cerevisiae for natural product discovery
topic Natural product discovery
Cross-species engineering
Spliceosome
High-throughput BGC cloning
Synthetic biology
Yeast
url http://www.sciencedirect.com/science/article/pii/S2405805X2100003X
work_keys_str_mv AT ziheliu expressionoffungalbiosyntheticgeneclustersinscerevisiaefornaturalproductdiscovery
AT zhenquanlin expressionoffungalbiosyntheticgeneclustersinscerevisiaefornaturalproductdiscovery
AT jensnielsen expressionoffungalbiosyntheticgeneclustersinscerevisiaefornaturalproductdiscovery