Biosynthesis of Fungal Natural Products Involving Two Separate Pathway Crosstalk

Fungal natural products (NPs) usually possess complicated structures, exhibit satisfactory bioactivities, and are an outstanding source of drug leads, such as the cholesterol-lowering drug lovastatin and the immunosuppressive drug mycophenolic acid. The fungal NPs biosynthetic genes are always arran...

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Main Authors: Guangzhi Dai, Qiyao Shen, Youming Zhang, Xiaoying Bian
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/8/3/320
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author Guangzhi Dai
Qiyao Shen
Youming Zhang
Xiaoying Bian
author_facet Guangzhi Dai
Qiyao Shen
Youming Zhang
Xiaoying Bian
author_sort Guangzhi Dai
collection DOAJ
description Fungal natural products (NPs) usually possess complicated structures, exhibit satisfactory bioactivities, and are an outstanding source of drug leads, such as the cholesterol-lowering drug lovastatin and the immunosuppressive drug mycophenolic acid. The fungal NPs biosynthetic genes are always arranged within one single biosynthetic gene cluster (BGC). However, a rare but fascinating phenomenon that a crosstalk between two separate BGCs is indispensable to some fungal dimeric NPs biosynthesis has attracted increasing attention. The hybridization of two separate BGCs not only increases the structural complexity and chemical diversity of fungal NPs, but also expands the scope of bioactivities. More importantly, the underlying mechanism for this hybridization process is poorly understood and needs further exploration, especially the determination of BGCs for each building block construction and the identification of enzyme(s) catalyzing the two biosynthetic precursors coupling processes such as Diels–Alder cycloaddition and Michael addition. In this review, we summarized the fungal NPs produced by functional crosstalk of two discrete BGCs, and highlighted their biosynthetic processes, which might shed new light on genome mining for fungal NPs with unprecedented frameworks, and provide valuable insights into the investigation of mysterious biosynthetic mechanisms of fungal dimeric NPs which are constructed by collaboration of two separate BGCs.
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spelling doaj.art-d3cc8795915c4ebabe2b3f3c9d6e44652023-11-30T21:05:49ZengMDPI AGJournal of Fungi2309-608X2022-03-018332010.3390/jof8030320Biosynthesis of Fungal Natural Products Involving Two Separate Pathway CrosstalkGuangzhi Dai0Qiyao Shen1Youming Zhang2Xiaoying Bian3Helmholtz International Lab for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, ChinaHelmholtz International Lab for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, ChinaHelmholtz International Lab for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, ChinaHelmholtz International Lab for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, ChinaFungal natural products (NPs) usually possess complicated structures, exhibit satisfactory bioactivities, and are an outstanding source of drug leads, such as the cholesterol-lowering drug lovastatin and the immunosuppressive drug mycophenolic acid. The fungal NPs biosynthetic genes are always arranged within one single biosynthetic gene cluster (BGC). However, a rare but fascinating phenomenon that a crosstalk between two separate BGCs is indispensable to some fungal dimeric NPs biosynthesis has attracted increasing attention. The hybridization of two separate BGCs not only increases the structural complexity and chemical diversity of fungal NPs, but also expands the scope of bioactivities. More importantly, the underlying mechanism for this hybridization process is poorly understood and needs further exploration, especially the determination of BGCs for each building block construction and the identification of enzyme(s) catalyzing the two biosynthetic precursors coupling processes such as Diels–Alder cycloaddition and Michael addition. In this review, we summarized the fungal NPs produced by functional crosstalk of two discrete BGCs, and highlighted their biosynthetic processes, which might shed new light on genome mining for fungal NPs with unprecedented frameworks, and provide valuable insights into the investigation of mysterious biosynthetic mechanisms of fungal dimeric NPs which are constructed by collaboration of two separate BGCs.https://www.mdpi.com/2309-608X/8/3/320biosynthetic pathway crosstalknatural productbiosynthetic gene clusterpolyketidefungibioactivity
spellingShingle Guangzhi Dai
Qiyao Shen
Youming Zhang
Xiaoying Bian
Biosynthesis of Fungal Natural Products Involving Two Separate Pathway Crosstalk
Journal of Fungi
biosynthetic pathway crosstalk
natural product
biosynthetic gene cluster
polyketide
fungi
bioactivity
title Biosynthesis of Fungal Natural Products Involving Two Separate Pathway Crosstalk
title_full Biosynthesis of Fungal Natural Products Involving Two Separate Pathway Crosstalk
title_fullStr Biosynthesis of Fungal Natural Products Involving Two Separate Pathway Crosstalk
title_full_unstemmed Biosynthesis of Fungal Natural Products Involving Two Separate Pathway Crosstalk
title_short Biosynthesis of Fungal Natural Products Involving Two Separate Pathway Crosstalk
title_sort biosynthesis of fungal natural products involving two separate pathway crosstalk
topic biosynthetic pathway crosstalk
natural product
biosynthetic gene cluster
polyketide
fungi
bioactivity
url https://www.mdpi.com/2309-608X/8/3/320
work_keys_str_mv AT guangzhidai biosynthesisoffungalnaturalproductsinvolvingtwoseparatepathwaycrosstalk
AT qiyaoshen biosynthesisoffungalnaturalproductsinvolvingtwoseparatepathwaycrosstalk
AT youmingzhang biosynthesisoffungalnaturalproductsinvolvingtwoseparatepathwaycrosstalk
AT xiaoyingbian biosynthesisoffungalnaturalproductsinvolvingtwoseparatepathwaycrosstalk