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新型 -AT 聚酮类化合物的发现、结构、生物活性和生物合成的最新进展。

Recent Advances in Discovery, Structure, Bioactivity, and Biosynthesis of -AT Polyketides.

机构信息

Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China.

College of Food Science and Engineering, Ningbo University, Ningbo, Zhejiang 315832, China.

出版信息

J Agric Food Chem. 2024 Oct 2;72(39):21318-21343. doi: 10.1021/acs.jafc.4c03750. Epub 2024 Sep 20.

DOI:10.1021/acs.jafc.4c03750
PMID:39302874
Abstract

Bacterial -acyltransferase polyketide synthases (-AT PKSs) are among the most complex enzymes, which are responsible for generating a wide range of natural products, identified as -AT polyketides. These polyketides have received significant attention in drug development due to their structural diversity and potent bioactivities. With approximately 300 synthesized molecules discovered so far, -AT PKSs are found widespread in bacteria. Their biosynthesis pathways exhibit considerable genetic diversity, leading to the emergence of numerous enzymes with novel mechanisms, serving as a valuable resource for genetic engineering aimed at modifying small molecules' structures and creating new engineered enzymes. Despite the systematic discussions on -AT polyketides and their biosynthesis in earlier studies, the continuous advancements in tools, methods, compound identification, and biosynthetic pathways require a fresh update on accumulated knowledge. This review seeks to provide a comprehensive discussion for the 27 types of -AT polyketides discovered within the last seven years, detailing their sources, structures, biological activities, and biosynthetic pathways. By reviewing this new knowledge, a more profound understanding of the -AT polyketide family can be achieved.

摘要

细菌酰基转移酶聚酮合酶(-AT PKSs)是最复杂的酶之一,负责生成广泛的天然产物,被鉴定为 -AT 聚酮类化合物。由于其结构多样性和强大的生物活性,这些聚酮类化合物在药物开发中受到了极大的关注。迄今为止,已经发现了大约 300 种合成分子,-AT PKSs 在细菌中广泛存在。它们的生物合成途径表现出相当大的遗传多样性,导致出现了许多具有新颖机制的酶,成为了用于修饰小分子结构和创造新工程酶的基因工程的宝贵资源。尽管早期的研究对 -AT 聚酮类化合物及其生物合成进行了系统的讨论,但工具、方法、化合物鉴定和生物合成途径的不断进步需要对积累的知识进行更新。本综述旨在为过去七年发现的 27 种 -AT 聚酮类化合物提供全面的讨论,详细介绍它们的来源、结构、生物活性和生物合成途径。通过回顾这些新知识,可以更深入地了解 -AT 聚酮类化合物家族。

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J Agric Food Chem. 2024 Oct 2;72(39):21318-21343. doi: 10.1021/acs.jafc.4c03750. Epub 2024 Sep 20.
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