Genome-based deletion analysis reveals the prenyl xanthone biosynthesis pathway in Aspergillus nidulans.

doi:10.1021/ja1096682

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標題:	Genome-based deletion analysis reveals the prenyl xanthone biosynthesis pathway in Aspergillus nidulans.
作者:	James, F.Sanchez Entwistle, Ruth Hung, Jui-Hsiang Yaegashi, Junko Jain, Sofina Chiang, Yi-Ming Clay, C.C.Wang Berl, R.Oakley
貢獻者:	生物科技系
關鍵字:	Secondary Metabolism Gene Clusters Synthase Fungi Prenyltransferases Variecolor Fumigatus Proteins
日期:	2011-05
上傳時間:	2013-06-05 16:42:47 (UTC+8)
出版者:	ACS Amer Chemical Soc
摘要:	Xanthones are a class of molecules that bind to a number of drug targets and possess a myriad of biological properties. An understanding of xanthone biosynthesis at the genetic level should facilitate engineering of second-generation molecules and increasing production of first-generation compounds. The filamentous fungus Aspergillus nidulans has been found to produce two prenylated xanthones, shamixanthone and emericellin, and we report the discovery of two more, variecoxanthone A and epishamixanthone. Using targeted deletions that we created, we determined that a cluster of 10 genes including a polyketide synthase gene, mdpG, is required for prenyl xanthone biosynthesis. mdpG was shown to be required for the synthesis of the anthraquinone emodin, monodictyphenone, and related compounds, and our data indicate that emodin and monodictyphenone are precursors of prenyl xanthones. Isolation of intermediate compounds from the deletion strains provided valuable clues as to the biosynthetic pathway, but no genes accounting for the prenylations were located within the cluster. To find the genes responsible for prenylation, we identified and deleted seven putative prenyltransferases in the A. nidulans genome. We found that two prenyltransferase genes, distant from the cluster, were necessary for prenyl xanthone synthesis. These genes belong to the fungal indole prenyltransferase family that had previously been shown to be responsible for the prenylation of amino acid derivatives. In addition, another prenyl xanthone biosynthesis gene is proximal to one of the prenyltransferase genes. Our data, in aggregate, allow us to propose a complete biosynthetic pathway for the A. nidulans xanthones.
關聯:	Journal of the American Chemical Society 133(11), pp.4010-4017
显示于类别:	[生物科技系(所)] 期刊論文

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