Assembly of aryl‐capped siderophores by modular peptide synthetases and polyketide synthases

Assembly of aryl‐capped siderophores by modular peptide synthetases and polyketide synthases
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通过模块化肽合成酶和聚酮合酶组装芳基封端的铁载体

DOI:
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发表时间:
2000
影响因子:
3.6
通讯作者:
L. Quadri
L. Quadri
中科院分区:
生物学2区
文献类型:
--
作者:
L. Quadri

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细菌铁载体帮助病原体在宿主体内获取铁。它们通常对于成功感染至关重要,它们的生物合成代表了一个有吸引力的抗生素靶标。最近,已经鉴定了几个铁载体生物合成位点,体外研究增进了我们对来自分枝杆菌属、假单胞菌属、耶尔森菌属的芳基封端肽和肽聚酮铁载体生物合成的认识。和其他细菌。这些研究还为相关铁载体和许多具有医学相关性的次级代谢物的组装提供了见解。芳基封端肽和肽聚酮铁载体的组装涉及非核糖体肽合成酶、聚酮合酶和非核糖体肽聚酮杂合亚基。对这些亚基的分析表明,它们的域和模块在功能和结构上是独立的。大自然似乎选择了一组功能域和模块,可以以不同的顺序和组合重新排列以生物合成不同的产品。尽管关于模块化合成酶和合成酶还有很多东西有待了解,但已经可以设想设计这些酶以产生新产品的策略。
Bacterial siderophores assist pathogens in iron acquisition inside their hosts. They are often essential for achieving a successful infection, and their biosynthesis represents an attractive antibiotic target. Recently, several siderophore biosynthetic loci have been identified, and in vitro studies have advanced our knowledge of the biosynthesis of aryl‐capped peptide and peptide–polyketide siderophores from Mycobacterium spp., Pseudomonas spp., Yersinia spp. and other bacteria. These studies also provided insights into the assembly of related siderophores and many secondary metabolites of medical relevance. Assembly of aryl‐capped peptide and peptide–polyketide siderophores involves non‐ribosomal peptide synthetase, polyketide synthase and non‐ribosomal‐peptide polyketide hybrid subunits. Analysis of these subunits suggests that their domains and modules are functionally and structurally independent. It appears that nature has selected a set of functional domains and modules that can be rearranged in different order and combinations to biosynthesize different products. Although much remains to be learned about modular synthetases and synthases, it is already possible to conceive strategies to engineer these enzymes to generate novel products.
DOI: 10.1016/s1367-5931(97)80067-1
发表时间: 1997-10
影响因子: 7.8
作者:
Christopher T. Walsh;A. M. Gehring;P. Weinreb;Luis E. N. Quadri;R. Flugel
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DOI: 10.1021/bi9719861
发表时间: 1998-02-10
期刊: BIOCHEMISTRY
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DOI: 10.1021/bi991787c
发表时间: 1999-11-09
期刊: BIOCHEMISTRY
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DOI: 10.1126/science.287.5453.640
发表时间: 2000-01-28
期刊: SCIENCE
影响因子: 56.9
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Tang, L;Shah, S;Julien, B
通讯作者: Julien, B
DOI: 10.1021/bi970453p
发表时间: 1997-07-15
期刊: BIOCHEMISTRY
影响因子: 2.9
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