The amide bond with its planarity and lack of chemical reactivity is at the heart of protein structure. Chemical methylation of amides is known but was considered too harsh to be accessible to biology. Until last year there was no protein structure in the data bank with an enzymatically methylated amide. The discovery that the natural macrocyclic product, omphalotin is ribosomally synthesized, was not as had been assumed by non-ribosomal peptide synthesis. This was the first definitive evidence that an enzyme could methylate the amide bond. The enzyme, OphMA, iteratively self-hypermethylates its own C-terminus using SAM as cofactor. A second enzyme OphP, a prolyl oligopeptidase cleaves the core peptide from OphMA and cyclizes it into omphalotin. The molecular mechanism for OphMA was elucidated by mutagenesis, structural, biochemical and theoretical studies. This review highlights current progress in peptide N-methylating enzymes.

具有平面性和缺乏化学反应性的酰胺键是蛋白质结构的核心。酰胺的化学甲基化是已知的，但被认为过于苛刻而无法用于生物学。直到去年，数据库中还没有含有酶促甲基化酰胺的蛋白质结构。天然大环产物 omphalotin 是核糖体合成的这一发现与非核糖体肽合成所假设的不同。这是酶可以甲基化酰胺键的第一个明确证据。酶 OphMA 使用 SAM 作为辅因子，反复自身超甲基化其自身的 C 端。第二种酶 OphP，一种脯氨酰寡肽酶从 OphMA 切割核心肽并将其环化为 omphalotin。OphMA 的分子机制通过诱变、结构、生化和理论研究。这篇综述强调了肽的当前进展N-甲基化酶。