Illuminating the Diversity of Aromatic Polyketide Synthases in Aspergillus nidulans

被引:151
作者
Ahuja, Manmeet [2 ]
Chiang, Yi-Ming [1 ,4 ]
Chang, Shu-Lin [3 ,4 ]
Praseuth, Mike B. [4 ]
Entwistle, Ruth [2 ]
Sanchez, James F. [4 ]
Lo, Hsien-Chun [4 ]
Yeh, Hsu-Hua [4 ,5 ]
Oakley, Berl R. [2 ]
Wang, Clay C. C. [4 ,6 ]
机构
[1] Chia Nan Univ Pharm & Sci, Grad Inst Pharmaceut Sci, Tainan 71710, Taiwan
[2] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA
[3] Chia Nan Univ Pharm & Sci, Dept Biotechnol, Tainan 71710, Taiwan
[4] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA
[5] Natl Chiao Tung Univ, Dept Biol Sci & Technol, Hsinchu 30010, Taiwan
[6] Univ So Calif, Dept Chem, Coll Letters Arts & Sci, Los Angeles, CA 90089 USA
关键词
GENE-CLUSTER; BIOSYNTHETIC-PATHWAY; ACID SYNTHASE; IDENTIFICATION; MEROTERPENOIDS; PRODUCT; NAPHTHOPYRONE; THIOESTERASE; METABOLITES; CYCLIZATION;
D O I
10.1021/ja3016395
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
Genome sequencing has revealed that fungi have the ability to synthesize many more natural products (NPs) than are currently known, but methods for obtaining suitable expression of NPs have been inadequate. We have developed a successful strategy that bypasses normal regulatory mechanisms. By efficient gene targeting, we have replaced, en masse, the promoters of nonreducing polyketide synthase (NR-PKS) genes, key genes in NP biosynthetic pathways, and other genes necessary for NR-PKS product formation or release. This has allowed us to determine the products of eight NR-PKSs of Aspergillus nidulans, including seven novel compounds, as well as the NR-PKS genes required for the synthesis of the toxins alternariol (8) and cichorine (19).
引用
收藏
页码:8212 / 8221
页数:10
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