Biosynthesis of Lincosamide Antibiotics: Reactions Associated with Degradation and Detoxification Pathways Play a Constructive Role,Accounts of Chemical Research

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Biosynthesis of Lincosamide Antibiotics: Reactions Associated with Degradation and Detoxification Pathways Play a Constructive Role
Accounts of Chemical Research ( IF 16.4 ) Pub Date : 2018-05-24 00:00:00 , DOI: 10.1021/acs.accounts.8b00135
Daozhong Zhang ₁ , Zhijun Tang ₁ , Wen Liu _{1,

2}

Affiliation

Natural products typically are small molecules produced by living organisms. These products possess a wide variety of biological activities and thus have historically played a critical role in medicinal chemistry and chemical biology either as chemotherapeutic agents or as useful tools. Natural products are not synthesized for use by human beings; rather, living organisms produce them in response to various biochemical processes and environmental concerns, both internal and external. These processes/concerns are often dynamic and thus motivate the diversification, optimization, and selection of small molecules in line with changes in biological function. Consequently, the interactions between living organisms and their environments serve as an engine that drives coevolution of natural products and their biological functions and ultimately programs the constant theme of small-molecule development in nature based on biosynthesis generality and specificity. Following this theme, we herein review the biosynthesis of lincosamide antibiotics and dissect the process through which nature creates an unusual eight-carbon aminosugar (lincosamide) and then functionalizes this common high-carbon chain-containing sugar core with diverse l-proline derivatives and sulfur appendages to form individual members, including the clinically useful anti-infective agent lincomycin A and its naturally occurring analogues celesticetin and Bu-2545.

中文翻译：

林可酰胺抗生素的生物合成：与降解和解毒途径相关的反应起建设性作用

天然产物通常是由生物体产生的小分子。这些产品具有广泛的生物学活性，因此在历史上一直作为药物或有用工具在药物化学和化学生物学中发挥关键作用。天然产物不是合成供人类使用的；相反，活有机体是根据内部和外部的各种生化过程和环境问题生产它们的。这些过程/关注点通常是动态的，因此会根据生物学功能的变化来激发小分子的多样化，优化和选择。所以，生命有机体与其环境之间的相互作用充当了驱动自然产物及其生物学功能共同进化的引擎，并最终根据生物合成的普遍性和特异性对自然界中小分子发展的恒定主题进行了编程。遵循这个主题，我们在本文中综述了林可酰胺抗生素的生物合成，并剖析了自然界产生不寻常的八碳氨基糖（林可酰胺）的过程，然后使这个常见的含高碳链糖核具有多种功能1-脯氨酸衍生物和硫附属物形成单个成员，包括临床上有用的抗感染药林可霉素A及其天然存在的类似物Celesticetin和Bu-2545。

更新日期：2018-05-24

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