S-腺苷-L-甲硫氨酸依赖的3-氨基-3-羧基丙基利用酶研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2023-0220

摘要/Abstract

摘要：

S-腺苷-L-甲硫氨酸（S-adenosyl-L-methionine，SAM）是生物体内重要的辅因子。SAM的结构中具有3个不稳定的C-S键，不同的SAM依赖酶能够选择性地切割其中不同的C-S键来催化各种类型的反应。其中，利用SAM甲基部分的甲基转移酶和腺苷部分的SAM自由基酶被广泛研究。UniProt数据库中保存了超过1 800 000条SAM依赖的甲基转移酶序列；SAM自由基酶也已经成为最大的酶家族之一，数目超过700 000个。但利用SAM中3-氨基-3羧基丙基（3-amino-3-carboxypropyl，ACP）的酶却报道相对较少，本文对目前这一类酶的研究进行分类介绍，并对这一领域未来研究方向进行展望。

关键词: S-腺苷-L-甲硫氨酸, 3-氨基-3-羧基丙基, 反应机制, 甲基转移酶, 非经典SAM自由基酶

Abstract:

S-adenosyl-L-methionine（SAM）is a very important cofactor in biology. It possesses three unstable C-S bonds, which can be selectively cleaved by various SAM-dependent enzymes, catalyzing a wide range of biochemical reactions. Methyltransferases and radical SAM enzymes, which cleave C-S bonds and use methyl and 5'-dexoyadenosine of SAM respectively, have been intensively studied. Over 1.8 million protein sequences of methyltransferases have been deposited in the UniProt database. Radical SAM enzymes have grown into one of the largest enzyme superfamilies, consisting of over 700 000 members. However, enzymes utilizing the 3-amino-3-carboxypropyl（ACP）group of SAM are relatively rarely reported. This paper aims to classify and introduce these enzymes while also provide a prospective research direction for the future.

Key words: S-adenosyl-L-methionine, 3-amino-3-carboxypropyl, reaction mechanism, methyltransferase, non-canonical radical SAM enzyme

何家乐, 董敏. S-腺苷-L-甲硫氨酸依赖的3-氨基-3-羧基丙基利用酶研究进展[J]. 生物技术通报, 2023, 39(12): 56-70.

HE Jia-le, DONG Min. Research Progress in S-adenosyl-L-methionine Dependent 3-amino-3-carboxypropyl Utilizing Enzymes[J]. Biotechnology Bulletin, 2023, 39(12): 56-70.

图/表 8

图1 SAM依赖酶催化的3种不同的C-S键断裂反应

Fig. 1 Three kinds of C-S bond cleavage reactions of SAM dependent enzymes

表1 ACP利用酶总结

Table 1 Summary of ACP utilizing enzymes

名称 Name	底物 Substrate	反应类型 Reaction
TYW2^[5]	4-去甲基丫苷	ACP转移反应（极性机理）
Tsr3^[6]	N¹-甲基假尿苷	ACP转移反应（极性机理）
YfiP^[7]	尿苷
NAS^[8]	氮杂环丁烷2-甲酸
MtNAS^[9]	谷氨酸
CntL^[10]	组氨酸
SPDS、SPMS^[11]	多胺
MccD^[12]	肽酰腺苷酸
NAT^[13]
BtaA^[14]	二酰甘油
Dph2^[15]	蛋白质翻译延伸因子2	ACP转移反应（自由基机理）
SbzP^[16]	β-NAD	ACP参与的环化反应
ACS、GnmY、ClbH^[17]	氨基环丙基-1-甲酸	ACP自身的环化反应
VioH、AzeJ^[18]	氮杂环丁烷2-甲酸

图2 参与RNA转录后修饰的ACP转移酶TYW2（a）, Tsr3（b）和YfiP（c）

Fig. 2 ACP transferase TYW2 (a), Tsr3 (b) and YfiP (c) involved in RNA modification

图3 烟草胺合酶（a）、热烟草胺合酶（b）与类烟草胺合酶（c）催化的反应

Fig. 3 Reactions catalyzed by NAS (a)、MtNAS (b) and CntL (c)

图4 其他极性机理的ACP转移酶

Fig. 4 ACP transferases with polar mechanism

图5 非经典SAM自由基酶Dph2的催化机理

Fig. 5 Catalytic mechanism of noncanonical radical SAM enzymme Dph2

图6 ACC合酶的催化机理及其他ACP环化酶催化的反应

Fig. 6 Catalytic mechanism of ACS and reactions catalyzed by ACP cyclases

图7 两种不同的氨基丙基修饰策略

Fig. 7 Two different strategies for aminopropyl modification

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