Shandong Key Laboratory of Applied Mycology, School of Life Sciences, Qingdao Agricultural University, 266109 Qingdao, China.
Chair of Technical Biochemistry, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany.
Nat Prod Rep. 2021 Sep 23;38(9):1555-1566. doi: 10.1039/d0np00099j.
Covering: up to the end of 2020Natural products bearing tetramic acid units as part of complex molecular architectures exhibit a broad range of potent biological activities. These compounds thus attract significant interest from both the biosynthetic and synthetic communities. Biosynthetically, most of the tetramic acids are derived from hybrid polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) machineries. To date, over 30 biosynthetic gene clusters (BGCs) involved in tetramate formation have been identified, from which different biosynthetic strategies evolved in Nature to assemble this intriguing structural unit were characterized. In this Highlight we focus on the biosynthetic concepts of tetramic acid formation and discuss the molecular mechanism towards selected representatives in detail, providing a systematic overview for the development of strategies for targeted tetramate genome mining and future applications of tetramate-forming biocatalysts for chemo-enzymatic synthesis.
截至 2020 年底 具有四氢酸单元的天然产物作为复杂分子结构的一部分，表现出广泛的强效生物活性。这些化合物因此引起了生物合成和合成两个领域的极大兴趣。在生物合成方面，大多数四氢酸来源于杂合聚酮合酶（PKS）和非核糖体肽合成酶（NRPS）机制。迄今为止，已经鉴定出 30 多个涉及四氢酸形成的生物合成基因簇（BGC），从中可以看出，自然界中已经进化出了不同的生物合成策略来组装这种有趣的结构单元。在这篇综述中，我们重点介绍四氢酸形成的生物合成概念，并详细讨论了一些代表性化合物的分子机制，为靶向四氢酸基因组挖掘策略的发展和未来四氢酸形成生物催化剂在化学酶合成中的应用提供了系统的概述。
