Graduate School of Engineering, Hokkaido University, Sapporo, Hokkaido, 060-8628, Japan.
Angew Chem Int Ed Engl. 2017 Feb 13;56(8):2026-2029. doi: 10.1002/anie.201611005. Epub 2017 Jan 18.
We recently discovered novel pseudotripeptides, the ketomemicins, which possess a C-terminal pseudodipeptide connected with a carbonylmethylene instead of an amide bond, through heterologous expression of gene clusters identified in actinobacteria. The carbonylmethylene structure is a stable isostere of the amide bond and its biological significance has been shown in several natural and synthetic products. Despite the biological importance of these compounds, little is known about how the carbonylmethylene structure is biosynthesized. In this work, we fully characterized the biosynthetic machinery of the pseudodipeptide. An aldolase, dehydratase, PLP-dependent glycine-C-acetyltransferase, and dehydrogenase were involved in the formation of the pseudodipeptide, with malonyl-CoA and phenylpyruvate as starter substrates.
我们最近通过异源表达放线菌中鉴定的基因簇发现了新型假三肽，即酮霉素，其 C 末端的假二肽通过羰基亚甲基而不是酰胺键连接，该羰基亚甲基结构是酰胺键的稳定等排体，其生物学意义已在几种天然和合成产物中得到证实。尽管这些化合物具有重要的生物学意义，但对于羰基亚甲基结构的生物合成知之甚少。在这项工作中，我们充分表征了假二肽的生物合成机制。醛缩酶、脱水酶、PLP 依赖性甘氨酸 C 乙酰基转移酶和脱氢酶参与了假二肽的形成，以丙二酰辅酶 A 和苯丙酮酸为起始底物。
