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天蓝色链霉菌放线紫红素生物合成基因簇的actVA区域的组织与功能

Organisation and functions of the actVA region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor.

作者信息

Caballero J L, Martinez E, Malpartida F, Hopwood D A

机构信息

John Innes Institute, John Innes Centre, Norwich, UK.

出版信息

Mol Gen Genet. 1991 Dec;230(3):401-12. doi: 10.1007/BF00280297.

DOI:10.1007/BF00280297
PMID:1766437
Abstract

Sequence analysis of the actVA region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor revealed a succession of six open reading frames (ORFs), all running in the same direction and extending over 5.32 kb. The protein product of actVA-ORF1 strongly resembles that of another gene, elsewhere in the act cluster (actII-ORF2), which codes for a trans-membrane protein previously implicated in actinorhodin export from the mycelium. This suggests that the two gene products may co-operate in actinorhodin export, perhaps being sufficient for self-protection of the organism against suicide. At least four of the other five ORFs are implicated in the control of the C-6 and C-8 ring-hydroxylation reactions, lacking in actVA mutants, that occur at middle to late stages in the actinorhodin biosynthetic pathway. This conclusion was reached by genetic mapping of actVA mutants to actVA-ORF3 and -ORF5 (and perhaps -ORF4), and by the finding of strong resemblances between the protein products of actVA-ORF2 and -ORF6 and the products of genes of the oxytetracycline or tetracenomycin gene clusters that have been implicated in ring-hydroxylation reactions in the biosynthesis of these other aromatic polyketide antibiotics.

摘要

天蓝色链霉菌放线紫红素生物合成基因簇的actVA区域的序列分析显示有六个开放阅读框(ORF)连续排列,它们均按同一方向延伸,长度超过5.32 kb。actVA-ORF1的蛋白质产物与act基因簇其他位置的另一个基因(actII-ORF2)的蛋白质产物极为相似,actII-ORF2编码一种跨膜蛋白,之前认为它参与了放线紫红素从菌丝体的输出过程。这表明这两种基因产物可能在放线紫红素的输出过程中协同作用,或许足以保护生物体免受自我伤害。在放线紫红素生物合成途径的中晚期发生C-6和C-8环羟基化反应,而actVA突变体中缺乏这些反应,其他五个ORF中至少有四个与这些反应的控制有关。得出这一结论的依据是,将actVA突变体基因定位到actVA-ORF3和-ORF5(可能还有-ORF4)上,以及发现actVA-ORF2和-ORF6的蛋白质产物与土霉素或四环素霉素基因簇中那些与这些其他芳香族聚酮类抗生素生物合成中环羟基化反应有关的基因产物有很强的相似性。

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