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曲霉次级代谢产物组的分子遗传挖掘:Emericellamide生物合成途径的发现。

Molecular genetic mining of the Aspergillus secondary metabolome: discovery of the emericellamide biosynthetic pathway.

作者信息

Chiang Yi-Ming, Szewczyk Edyta, Nayak Tania, Davidson Ashley D, Sanchez James F, Lo Hsien-Chun, Ho Wen-Yueh, Simityan Hagop, Kuo Eric, Praseuth Alex, Watanabe Kenji, Oakley Berl R, Wang Clay C C

机构信息

Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.

出版信息

Chem Biol. 2008 Jun;15(6):527-32. doi: 10.1016/j.chembiol.2008.05.010.

DOI:10.1016/j.chembiol.2008.05.010
PMID:18559263
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2494592/
Abstract

The recently sequenced genomes of several Aspergillus species have revealed that these organisms have the potential to produce a surprisingly large range of natural products, many of which are currently unknown. We have found that A. nidulans produces emericellamide A, an antibiotic compound of mixed origins with polyketide and amino acid building blocks. Additionally, we describe the discovery of four previously unidentified, related compounds that we designate emericellamide C-F. Using recently developed gene targeting techniques, we have identified the genes involved in emericellamide biosynthesis. The emericellamide gene cluster contains one polyketide synthase and one nonribosomal peptide synthetase. From the sequences of the genes, we are able to deduce a biosynthetic pathway for the emericellamides. The identification of this biosynthetic pathway opens the door to engineering novel analogs of this structurally complex metabolite.

摘要

最近对几种曲霉菌种进行测序的基因组显示,这些生物体有潜力产生一系列惊人的天然产物,其中许多目前还不为人知。我们发现构巢曲霉能产生埃默里卡酰胺A,这是一种由聚酮化合物和氨基酸构建单元组成的混合来源的抗生素化合物。此外,我们描述了四种先前未鉴定出的相关化合物的发现,我们将其命名为埃默里卡酰胺C - F。利用最近开发的基因靶向技术,我们确定了参与埃默里卡酰胺生物合成的基因。埃默里卡酰胺基因簇包含一个聚酮合酶和一个非核糖体肽合成酶。从这些基因的序列中,我们能够推断出埃默里卡酰胺的生物合成途径。这条生物合成途径的确定为构建这种结构复杂的代谢物的新型类似物打开了大门。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88bb/2494592/4c7fbb5e0d9a/nihms56867f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88bb/2494592/0bacc2d6a0ed/nihms56867f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88bb/2494592/91564fd0c06c/nihms56867f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88bb/2494592/4c7fbb5e0d9a/nihms56867f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88bb/2494592/0bacc2d6a0ed/nihms56867f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88bb/2494592/91564fd0c06c/nihms56867f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88bb/2494592/4c7fbb5e0d9a/nihms56867f3.jpg

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