Sequencing and analysis of the biosynthetic gene cluster of the lipopeptide antibiotic friulimicin in Actinoplanes friuliensis
Sequencing and analysis of the biosynthetic gene cluster of the lipopeptide antibiotic friulimicin in Actinoplanes friuliensis
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DOI：
10.1128/aac.00942-06
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发表时间：
2007-03-01
影响因子：
4.9
通讯作者：
Schwartz, D.
中科院分区：
文献类型：
--
作者：
Mueller, C.;Nolden, S.;Schwartz, D.
弗鲁利游动放线菌产生脂肽抗生素弗鲁利米星，其是具有连接至支链脂肪酸酰基残基的一个环外氨基酸的环状肽。与达托霉素的结构关系和弗留利霉素优异的抗菌性能使该抗生素成为有吸引力的候选药物。该基因簇由24个开放阅读框组成。fruiliensis进行测序分析。除了调控、自身抗性和运输基因外，该簇还包含编码肽合成酶的基因、参与抗生素脂肪酸组分合成和连接的蛋白质以及参与非蛋白质氨基酸哌啶酸、甲基天冬氨酸和2，3-二氨基丁酸合成的蛋白质。利用异源基因在大肠杆菌中的表达，我们提供了生化证据的立体选择性合成L-哌啶酸的赖氨酸环脱氨酶基因pip的推导蛋白。此外，我们表明参与的dabA和dabB基因的生物合成的2，3-二氨基丁酸的基因失活和随后的喂养实验。
Actinoplanes fruliensis produces the lipopeptide antibiotic friulimicin, which is a cyclic peptide with one exocyclic amino acid linked to a branched-chain fatty acid acyl residue. The structural relationship to daptomycin and the excellent antibacterial performance of friulimicin make the antibiotic an attractive drug candidate. The complete friulimicin biosynthetic gene cluster of 24 open reading frames from A. fruiliensis was sequenced and analyzed. In addition to genes for regulation, self-resistance, and transport, the cluster contains genes encoding peptide synthetases, proteins involved in the synthesis and linkage of the fatty acid component of the antibiotic, and proteins involved in the synthesis of the nonproteinogenic amino acids pipecolinic acid, methylaspartic acid, and 2,3-diaminobutyric acid. By using heterologous gene expression in Escherichia coli, we provide biochemical evidence for the stereoselective synthesis of L-pipecolinic acid by the deduced protein of the lysine cyclodeaminase gene pip. Furthermore, we show the involvement of the dabA and dabB genes in the biosynthesis of 2,3-diaminobutyric acid by gene inactivation and subsequent feeding experiments.