Heath Richard J, Rock Charles O
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Nat Prod Rep. 2002 Oct;19(5):581-96. doi: 10.1039/b110221b.
The mechanism for carbon-carbon bond formation used in the biosynthesis of natural products such as fatty acids and polyketides is a decarboxylating Claisen condensation. The enzymes that catalyze this reaction in various bacterial systems, collectively referred to as condensing enzymes, have been intensively studied in the past several decades, and members of the family have been crystallized. The condensing enzymes share a common 3-dimensional fold, first described for the biosynthetic thiolase I that catalyzes a non-decarboxylating Claisen condensation, although they share little similarity at the amino acid level. Their active sites, however, possess significant similarities. The initiation condensing enzymes use CoA primers and possess a catalytic triad of Cys, His, Asn; and the elongating condensing enzymes that exclusively use ACP thioesters have a triad of Cys, His, His. These active site differences affect the sensitivity of the respective enzymes to the antibiotics thiolactomycin and cerulenin. Different reaction mechanisms have been proposed for the condensing enzymes. This review covers the recent structural and mechanistic data to see if a unifying hypothesis for the reaction mechanism catalyzed by this important family of enzymes can be established.
在脂肪酸和聚酮化合物等天然产物生物合成中用于碳 - 碳键形成的机制是一种脱羧克莱森缩合反应。在各种细菌系统中催化该反应的酶统称为缩合酶，在过去几十年中已得到深入研究，并且该家族的成员已被结晶。缩合酶具有共同的三维折叠结构，最初是针对催化非脱羧克莱森缩合反应的生物合成硫解酶I描述的，尽管它们在氨基酸水平上几乎没有相似性。然而，它们的活性位点具有显著的相似性。起始缩合酶使用辅酶A引物，具有由半胱氨酸、组氨酸、天冬酰胺组成的催化三联体；而专门使用酰基载体蛋白硫酯的延伸缩合酶具有由半胱氨酸、组氨酸、组氨酸组成的三联体。这些活性位点的差异影响了各自的酶对抗生素硫内酯霉素和浅蓝菌素的敏感性。针对缩合酶提出了不同的反应机制。本综述涵盖了最近的结构和机制数据，以探讨是否可以为这一重要酶家族催化的反应机制建立一个统一的假说。
