Mechanism and Engineering of Polyketide Chain Initiation in Fredericamycin Biosynthesis

Mechanism and Engineering of Polyketide Chain Initiation in Fredericamycin Biosynthesis
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DOI:
10.1021/ja102517q
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发表时间:
2010-07-07
影响因子:
15
通讯作者:
Khosla, Chaitan
Khosla, Chaitan
中科院分区:
化学1区
文献类型:
--
作者:
Das, Abhirup;Szu, Ping-Hui;Khosla, Chaitan

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通过使用专用的起始聚酮合酶 (PKS) 模块整合非典型引物单元的能力为扩展聚酮天然产物的分子多样性提供了机会。 Here we identify the initiation PKS module responsible for hexadienyl priming of the antibiotic fredericamycin and investigate its biochemical properties.我们还利用该 PKS 模块来设计和体内生物合成代表性聚酮产品的异常引发类似物,从而强调其对代谢工程师的实用性。
The ability to incorporate atypical primer units through the use of dedicated initiation polyketide synthase (PKS) modules offers opportunities to expand the molecular diversity of polyketide natural products. Here we identify the initiation PKS module responsible for hexadienyl priming of the antibiotic fredericamycin and investigate its biochemical properties. We also exploit this PKS module for the design and in vivo biosynthesis of unusually primed analogues of a representative polyketide product, thereby emphasizing its utility to the metabolic engineer.