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海洋来源真菌中 的异表达触发次生代谢物生物合成基因的上调。

Heteroexpression of in Marine-Derived Fungi Triggers Upregulation of Secondary Metabolite Biosynthetic Genes.

机构信息

Ocean College, Zhejiang University, Zhoushan 316021, China.

出版信息

Mar Drugs. 2020 Dec 18;18(12):652. doi: 10.3390/md18120652.

DOI:10.3390/md18120652
PMID:33352941
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7766385/
Abstract

Fungi are a prospective resource of bioactive compounds, but conventional methods of drug discovery are not effective enough to fully explore their metabolic potential. This study aimed to develop an easily attainable method to elicit the metabolic potential of fungi using as a transcription regulation tool. In this study, functional analysis of (AnLaeA) and sp. Z5 (Az5LaeA) was done in the fungus sp. Z5. Heterologous AnLaeA-and native Az5LaeA-overexpression exhibited similar phenotypic effects and caused an increase in production of a bioactive compound diorcinol in sp. Z5, which proved the conserved function of this global regulator. In particular, heteroexpression of AnLaeA showed a significant impact on the expression of velvet complex genes, diorcinol synthesis-related genes, and different transcription factors (TFs). Moreover, heteroexpression of AnLaeA influenced the whole genome gene expression of sp. Z5 and triggered the upregulation of many genes. Overall, these findings suggest that heteroexpression of AnLaeA in fungi serves as a simple and easy method to explore their metabolic potential. In relation to this, AnLaeA was overexpressed in the fungus sp. LC1-4, which resulted in increased production of quinolactacin A.

摘要

真菌是生物活性化合物的潜在资源,但传统的药物发现方法还不够有效,无法充分挖掘其代谢潜力。本研究旨在开发一种简单易行的方法,利用 作为转录调控工具来挖掘真菌的代谢潜力。本研究在真菌 中对 (AnLaeA)和 sp. Z5 (Az5LaeA)进行了功能分析。在 中过表达异源 AnLaeA 和天然 Az5LaeA 表现出相似的表型效应,并导致生物活性化合物二奥醇的产量增加,证明了这个全局调控因子的保守功能。特别是,AnLaeA 的异源表达对 velvet 复合物基因、二奥醇合成相关基因和不同转录因子(TFs)的表达有显著影响。此外,AnLaeA 的异源表达还影响了 sp. Z5 的全基因组基因表达,并触发了许多基因的上调。总的来说,这些发现表明,在真菌中过表达 AnLaeA 是一种简单易行的方法,可以探索其代谢潜力。在此基础上,AnLaeA 在真菌 sp. LC1-4 中过表达,导致喹诺拉菌素 A 的产量增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/59937b7589e5/marinedrugs-18-00652-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/953d0b1cca02/marinedrugs-18-00652-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/705ae2fd5c0c/marinedrugs-18-00652-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/b888d353a06f/marinedrugs-18-00652-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/59937b7589e5/marinedrugs-18-00652-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/05ad6d7a48e1/marinedrugs-18-00652-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/0fe1aec1a1c4/marinedrugs-18-00652-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/226e29801007/marinedrugs-18-00652-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/79bc2ed2a88b/marinedrugs-18-00652-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/953d0b1cca02/marinedrugs-18-00652-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/705ae2fd5c0c/marinedrugs-18-00652-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/b888d353a06f/marinedrugs-18-00652-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd1/7766385/59937b7589e5/marinedrugs-18-00652-g008.jpg

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