阿维链霉菌
阿维菌素
伊维菌素
聚酮合酶
聚酮
化学
抗寄生虫的
盘尾丝虫病
链霉菌
抗寄生虫药
抗生素
微生物学
药理学
细菌
生物
生物化学
兽医学
生物合成
酶
医学
遗传学
免疫学
病理
解剖
作者
Sibylle Gaisser,Laurenz Kellenberger,Andrew L. Kaja,Alison J. Weston,Rachel E. Lill,Gabriele Wirtz,Steven G. Kendrew,Lindsey Low,Rose Sheridan,Barrie Wilkinson,I S Galloway,Kim Stutzman‐Engwall,Hamish A. I. McArthur,James Staunton,Peter F. Leadlay
摘要
Ivermectin™, a mixture of 22,23-dihydroavermectin B1a 9 with minor amounts of 22,23-dihydroavermectin B1b 10, is one of the most successful veterinary antiparasitic drugs ever produced. In humans, ivermectin has been used for the treatment of African river blindness (onchocerciasis) resulting in an encouraging decrease in the prevalence of skin and eye diseases linked to this infection. The components of ivermectin are currently synthesized by chemical hydrogenation of a specific double bond at C22–C23 in the polyketide macrolides avermectins B1a 5 and B1b 6, broad-spectrum antiparasitic agents isolated from the soil bacterium Streptomyces avermitilis. We describe here the production of such compounds (22,23-dihydroavermectins B1a 9 and A1a 11) by direct fermentation of a recombinant strain of S. avermitilis containing an appropriately-engineered polyketide synthase (PKS). This suggests the feasibility of a direct biological route to this valuable drug.
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