Deciphering chemical logic of fungal natural product biosynthesis through heterologous expression and genome mining

被引:34
作者
Chiang, Chen-Yu [1 ]
Ohashi, Masao [1 ]
Tang, Yi [1 ,2 ]
机构
[1] Dept Chem & Biomol Engn, 5531 Boelter Hall,420 Westwood Plaza, Los Angeles, CA 90095 USA
[2] Dept Chem & Biochem, 5531 Boelter Hall,420 Westwood Plaza, Los Angeles, CA 90095 USA
关键词
ITERATIVE POLYKETIDE SYNTHASES; RESORCYLIC ACID LACTONES; GENE-CLUSTER; ASPERGILLUS-NIDULANS; DEPENDENT ENZYME; PKS-NRPS; FUNCTIONAL-CHARACTERIZATION; SECONDARY METABOLITES; BIOCHEMICAL BASIS; FUSARIC ACID;
D O I
10.1039/d2np00050d
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Covering: 2010 to 2022 Heterologous expression of natural product biosynthetic gene clusters (BGCs) has become a widely used tool for genome mining of cryptic pathways, bottom-up investigation of biosynthetic enzymes, and engineered biosynthesis of new natural product variants. In the field of fungal natural products, heterologous expression of a complete pathway was first demonstrated in the biosynthesis of tenellin in Aspergillus oryzae in 2010. Since then, advances in genome sequencing, DNA synthesis, synthetic biology, etc. have led to mining, assignment, and characterization of many fungal BGCs using various heterologous hosts. In this review, we will highlight key examples in the last decade in integrating heterologous expression into genome mining and biosynthetic investigations. The review will cover the choice of heterologous hosts, prioritization of BGCs for structural novelty, and how shunt products from heterologous expression can reveal important insights into the chemical logic of biosynthesis. The review is not meant to be exhaustive but is rather a collection of examples from researchers in the field, including ours, that demonstrates the usefulness and pitfalls of heterologous biosynthesis in fungal natural product discovery.
引用
收藏
页码:89 / 127
页数:39
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