Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.
J Ind Microbiol Biotechnol. 2021 Jun 4;48(3-4). doi: 10.1093/jimb/kuab001.
Sulfonamides and sulfamates are a group of organosulfur compounds that contain the signature sulfamoyl structural motif. These compounds were initially only known as synthetic antibacterial drugs but were later also discovered as natural products. Eight highly potent examples have been isolated from actinomycetes to date, illustrating the large biosynthetic repertoire of this bacterial genus. For the biosynthesis of these compounds, several distinct and unique biosynthetic machineries have been discovered, capable to generate the unique S-N bond. For the creation of novel, second generation natural products by biosynthetic engineering efforts, a detailed understanding of the underlying enzyme machinery toward potent structural motifs is crucial. In this review, we aim to summarize the current state of knowledge on sulfonamide and sulfamate biosynthesis. A detailed discussion for the secondary sulfamate ascamycin, the tertiary sulfonamide sulfadixiamycin A, and the secondary sulfonamide SB-203208 is provided and their bioactivities and mode of actions are discussed.
磺胺类和磺胺酸盐是一类含有磺酰氨基结构特征的有机硫化合物。这些化合物最初仅作为合成抗菌药物而被知晓，但后来也被发现是天然产物。迄今为止，已经从放线菌中分离出八种高活性的实例，这说明了这类细菌属具有很大的生物合成潜力。对于这些化合物的生物合成，已经发现了几种不同且独特的生物合成机制，能够生成独特的 S-N 键。对于通过生物合成工程努力创造新型第二代天然产物，详细了解潜在的酶机制对于强效结构基序至关重要。在这篇综述中，我们旨在总结磺胺类和磺胺酸盐生物合成的最新知识。我们详细讨论了二级磺胺酸盐 ascamycin、三级磺胺酰胺 sulfadixiamycin A 和二级磺胺 SB-203208，并讨论了它们的生物活性和作用模式。
