Characterization of the biosynthetic gene cluster for the antifungal polyketide soraphen A from Sorangium cellulosum So ce26
Characterization of the biosynthetic gene cluster for the antifungal polyketide soraphen A from Sorangium cellulosum So ce26
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DOI：
10.1016/s0378-1119(02)00396-7
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发表时间：
2002-02-20
期刊：
影响因子：
3.5
通讯作者：
Schupp, T
中科院分区：
文献类型：
--
作者：
Ligon, J;Hill, S;Schupp, T
从纤维堆囊菌So ce 26中克隆了一个80 kb以上的基因组DNA区域，该区域包含用于合成抗真菌聚酮代谢物soraphen A的完整生物合成基因簇。测定了Soraphen A基因67，523 bp的核苷酸序列。该序列的检查导致两个相邻的I型聚酮合酶（PKS）基因编码的soraphen合酶的鉴定。其中一个soraphen A PKS基因包括三个生物合成模块，第二个包含五个额外的模块，总共八个。预测的酰基转移酶（AT）结构域的底物特异性，以及每个模块内鉴定的还原环结构域，与soraphen A结构的预期一致。在两个soraphen合酶基因的侧翼区域中鉴定了基因，这两个基因被认为在soraphen A的生物合成中起作用。soraphen PKS基因的下游是O-甲基转移酶（OMT）。在soraphen PKS基因的上游有一个编码还原酶的基因和一组被认为在甲氧丙二酰-酰基载体蛋白（ACP）的合成中起作用的基因。这种不寻常的扩展单元被建议纳入索拉芬聚酮链的两个位置。该组中的一个基因包含AT、ACP和OMT的不同结构域。(C)2002 Elsevier Science B. V.保留所有权利。
A genomic DNA region of over 80 kb that contains the complete biosynthetic gene cluster for the synthesis of the antifungal polyketide metabolite soraphen A was cloned from Sorangium cellulosum So ce26. The nucleotide sequence of the soraphen A gene region, including 67,523 bp was determined. Examination of this sequence led to the identification of two adjacent type I polyketide synthase (PKS) genes that encode the soraphen synthase. One of the soraphen A PKS genes includes three biosynthetic modules and the second contains five additional modules for a total of eight. The predicted substrate specificities of the acyltransferase (AT) domains, as well as the reductive loop domains identified within each module, are consistent with expectations from the structure of soraphen A. Genes were identified in the regions flanking the two soraphen synthase genes that are proposed to have roles in the biosynthesis of soraphen A. Downstream of the soraphen PKS genes is an O-methyltransferase (OMT) gone. Upstream of the soraphen PKS genes there is a gene encoding a reductase and a group of genes that are postulated to have roles in the synthesis of methoxymalonyl-acyl carrier protein (ACP). This unusual extender unit is proposed to be incorporated in two positions of the soraphen polyketide chain. One of the genes in this group contains distinct domains for an AT, an ACP, and an OMT. (C) 2002 Elsevier Science B.V. All rights reserved.