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解析脱氮嘌呤生物合成:吡咯并嘧啶核苷toyocamycin和sangivamycin的合成途径。

Deciphering deazapurine biosynthesis: pathway for pyrrolopyrimidine nucleosides toyocamycin and sangivamycin.

作者信息

McCarty Reid M, Bandarian Vahe

机构信息

Department of Biochemistry and Molecular Biophysics, University of Arizona, 1041 E. Lowell Street, Tucson, AZ 85721, USA.

出版信息

Chem Biol. 2008 Aug 25;15(8):790-8. doi: 10.1016/j.chembiol.2008.07.012.

Abstract

Pyrrolopyrimidine nucleosides analogs, collectively referred to as deazapurines, are an important class of structurally diverse compounds found in a wide variety of biological niches. In this report, a cluster of genes from Streptomyces rimosus (ATCC 14673) involved in production of the deazapurine antibiotics sangivamycin and toyocamycin was identified. The cluster includes toyocamycin nitrile hydratase, an enzyme that catalyzes the conversion of toyocamycin to sangivamycin. In addition to this rare nitrile hydratase, the cluster encodes a GTP cyclohydrolase I, linking the biosynthesis of deazapurines to folate biosynthesis, and a set of purine salvage/biosynthesis genes, which presumably convert the guanine moiety from GTP to the adenine-like deazapurine base found in toyocamycin and sangivamycin. The gene cluster presented here could potentially serve as a model to allow identification of deazapurine biosynthetic pathways in other bacterial species.

摘要

吡咯并嘧啶核苷类似物,统称为脱氮嘌呤,是一类重要的结构多样的化合物,存在于各种各样的生物生态位中。在本报告中,鉴定了来自龟裂链霉菌(ATCC 14673)的一组参与脱氮嘌呤抗生素桑吉瓦霉素和丰加霉素生产的基因。该基因簇包括丰加霉素腈水合酶,一种催化丰加霉素转化为桑吉瓦霉素的酶。除了这种罕见的腈水合酶外,该基因簇还编码一种GTP环水解酶I,将脱氮嘌呤的生物合成与叶酸生物合成联系起来,以及一组嘌呤补救/生物合成基因,这些基因可能将GTP中的鸟嘌呤部分转化为丰加霉素和桑吉瓦霉素中发现的腺嘌呤样脱氮嘌呤碱基。此处呈现的基因簇可能潜在地用作模型,以鉴定其他细菌物种中的脱氮嘌呤生物合成途径。

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