白色链霉菌JA3453中垩唑霉素生物合成基因簇甲氧丙二酰ACP生物合成基因ozmF的遗传分析  

Genetic Analysis of Gene ozmF in Methoxymalonyl-ACP Biosynthesis Locus of OZM Biosynthetic Gene Cluster in S.albus JA3453

作　　者：赵春华[1] 宋丹凤[1] 周秀芬[1] 沈奔[2] 邓子新[1] 

机构地区：[1]上海交通大学教育部代谢工程重点实验室,上海200030 [2]威斯康星大学Madison分校化学系

出　　处：《上海交通大学学报（农业科学版）》2008年第1期17-19,24,共4页Journal of Shanghai Jiaotong University(Agricultural Science)

摘　　要：恶唑霉素(oxazolomycin,OZM)是由白色链霉菌JA3453产生的杂合聚酮聚肽抗生素,其结构特征为螺旋链接的-β内酯/-γ内酰胺,垩唑环,(E,E)二烯和(Z,Z,E)三烯链。恶唑霉素具有抗肿瘤,抗病毒和一定的抗细菌的生物活性。前面工作中我们已经从白色链霉菌JA3453中定位了135 kb的DNA区域,这个区域覆盖了整个ozm基因簇,对部分片段测序揭示了负责甲氧丙二酰ACP生物合成位点的6个基因。本文通过突变以及互补分析其中的甲基转移酶基因ozmF并证实其与恶唑霉素生物合成相关。这些结论有助于我们通过组合生物化学的方法产生新的OZM衍生物。Oxazolomycin（OZM）, produced by Streptomyces albus JA3453, is a hybrid peptide-polyketide antibiotic structurally characterized by a unique spiro-linked β-lactone/γ-lactam moiety, an oxazole ring, an （E, E）-diene, and a （Z, Z, E）-triene chain. OZM exhibits potent antitumor, antiviral, and limited antibacterial activities. In previous study we have localized a 135 kb DNA region from S. albus JA3453 covering the entire OZM biosynthetic genc cluster. Sequence analysis of this fragment revealed six genes likely responsible for methoxymalonyl-ACP biosynthesis. The involvement of the latter in OZM biosynthesis was proven directly by mutational and complementary analysis of selected genes, ozmF encoding a methyhransferasc within this locus. These results have now set the stage for generation of novel OZM analogs by combinatorial biosynthesis methods in S. albuz.

关 键 词：杂合聚酮聚肽 恶唑霉素 甲氧丙二酰ACP生物合成位点 

分 类 号：Q939.93[生物学—微生物学]