Mycofactocin Biosynthesis Proceeds through 3-Amino-5-[(p-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone (AHDP); Direct Observation of MftE Specificity toward MftA*,Biochemistry

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Mycofactocin Biosynthesis Proceeds through 3-Amino-5-[(p-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone (AHDP); Direct Observation of MftE Specificity toward MftA*
Biochemistry ( IF 2.9 ) Pub Date : 2018-09-05 00:00:00 , DOI: 10.1021/acs.biochem.8b00816
Richard Ayikpoe ₁ , Joe Salazar ₁ , Brian Majestic ₁ , John A. Latham ₁

Affiliation

The structure of the ribosomally synthesized and post-translationally modified peptide product mycofactocin is unknown. Recently, the first step in mycofactocin biosynthesis was shown to be catalyzed by MftC in two S-adenosylmethionine-dependent steps. In the first step, MftC catalyzes the oxidative decarboxylation of the MftA peptide to produce the styrene-containing intermediate MftA**, followed by a subsequent C–C bond formation to yield the lactam-containing MftA*. Here, we demonstrate the subsequent biosynthetic step catalyzed by MftE is specific for MftA*. The hydrolysis of MftA* leads to the formation of MftA(1–28) and 3-amino-5-[(p-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone (AHDP). The hydrolysis reaction is Fe²⁺-dependent, and addition of the metal to the reaction mixture leads to a k_obs of ∼0.2 min^–1. Lastly, we validate the structure of AHDP by ¹H, ¹³C, and COSY nuclear magnetic resonance techniques as well as mass spectrometry.

中文翻译：

通过3-氨基-5-[（对羟基苯基）甲基] -4,4-二甲基-2-吡咯烷酮（AHDP）进行霉菌素的生物合成。直接观察MftE对MftA的特异性*

核糖体合成和翻译后修饰的肽产物霉菌因子的结构是未知的。最近，已证明MftC可以在两个S-腺苷甲硫氨酸依赖性步骤中催化霉菌素生物合成的第一步。第一步，MftC催化MftA肽的氧化脱羧反应，生成含苯乙烯的中间体MftA **，随后进行C–C键形成，生成含内酰胺的MftA *。在这里，我们证明了由MftE催化的后续生物合成步骤对MftA *具有特异性。MftA *的水解导致MftA（1-28）和3-氨基-5-[（对羟基苯基）甲基] -4,4-二甲基-2-吡咯烷酮（AHDP）的形成。水解反应为Fe ²⁺依赖，并且将金属添加到反应混合物中会导致〜0.2 min ^–1的k _obs。最后，我们通过¹ H，¹³ C和COZY核磁共振技术以及质谱对AHDP的结构进行了验证。

更新日期：2018-09-05

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