Functional Expression of Genes Involved in the Biosynthesis of the Novel Polyketide Chain Extension Unit, Methoxymalonyl-Acyl Carrier Protein, and Engineered Biosynthesis of 2-Desmethyl-2-Methoxy-6-De

详细信息    查看全文

• 作者：Yasuo Kato ; Linquan Bai ; Qun Xue ; W. Peter Revill ; Tin-Wein Yu ; and Heinz G. Floss
• 刊名：Journal of the American Chemical Society
• 出版年：2002
• 出版时间：May 15, 2002
• 年：2002
• 卷：124
• 期：19
• 页码：5268 - 5269
• 全文大小：45K
• 年卷期：v.124,no.19(May 15, 2002)
• ISSN：1520-5126

文摘

A subcluster of five genes, asm13-17, from the ansamitocin biosynthetic gene cluster of Actinosynnema pretiosum was coexpressed in Streptomyces lividans with the genes encoding the 6-deoxyerythronolide B (6-DEB) synthase from Saccharopolyspora erythraea, in which the methylmalonate-specifying AT6 domain had been replaced by the methoxymalonate-specifying AT8 domain from the FK520 cluster of Streptomyces hygroscopicus. The engineered strain produced the predicted product, 2-desmethyl-2-methoxy-DEB, instead of 6-DEB and 2-desmethyl-6-DEB, which were formed in the absence of the asm13-17 cassette, indicating that asm13-17 are sufficient for synthesis of this unusual chain extension unit. Deletion of asm17, encoding a methyltransferase, from the cassette gave 6-DEB instead of its hydroxy analogue, indicating that methylation of the extender unit is required for its incorporation.