An Efficient System for Heterologous Expression of Secondary Metabolite Genes in Aspergillus nidulans

doi:10.1021/ja401945a

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標題:	An Efficient System for Heterologous Expression of Secondary Metabolite Genes in Aspergillus nidulans
作者:	Chiang, Yi-Ming Oakley, C. Elizabeth Ahuja, Manmeet Entwistle, Ruth Schultz, Aric Chang, Shu-Lin Sung, Calvin T. Wang, Clay C. C. Oakley, Bed R.
貢獻者:	藥學系
關鍵字:	Polyketide Synthase Gene Natural-Products Biosynthetic-Pathway Combinatorial Chemistry Cluster Oryzae Identification Acid Fumigatus Reveals
日期:	2013-05
上傳時間:	2014-05-26 10:43:03 (UTC+8)
出版者:	Amer Chemical Soc
摘要:	Fungal secondary metabolites (SMs) are an important source of medically valuable compounds. Genome projects have revealed that fungi have many SM biosynthetic gene clusters that are not normally expressed. To access these potentially valuable, cryptic clusters, we have developed a heterologous expression system in Aspergillus nidulans. We have developed an efficient system for amplifying genes from a target fungus, placing them under control of a regulatable promoter, transferring them into A. nidulans, and expressing them. We have validated this system by expressing nonreducing polyketide synthases of Aspergillus terreus and additional genes required for compound production and release. We have obtained compound production and release from six of these nonreducing polyketide synthases and have identified the products. To demonstrate that the procedure allows transfer and expression of entire secondary metabolite biosynthetic pathways, we have expressed all the genes of a silent A terreus cluster and demonstrate that it produces asperfuranone. Further, by expressing the genes of this pathway in various combinations, we have clarified the asperfuranone biosynthetic pathway. We have also developed procedures for deleting entire A nidulans SM clusters. This allows us to remove clusters that might interfere with analyses of heterologously expressed genes and to eliminate unwanted toxins.
關聯:	Journal of the American Chemical Society, v.135 n.20 pp.7720-7731
显示于类别:	[藥學系(所)] 期刊論文

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