腐胺<i>C-</i>和<i>N-</i>羟化酶的功能鉴定,ACS Chemical Biology

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腐胺C-和N-羟化酶的功能鉴定
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2016-08-24 00:00:00 , DOI: 10.1021/acschembio.6b00629
Bin Li , Tiffany Lowe-Power ₁ , Shin Kurihara , Stephen Gonzales , Jacinth Naidoo , John B. MacMillan , Caitilyn Allen ₁ , Anthony J. Michael

Affiliation

小的多胺腐胺（1,4-二氨基丁烷）在生活的所有三个领域中普遍存在。它是一种前体，通过Ñ -aminopropylation或Ñ -aminobutylation，对于较长多胺的生物合成亚精胺，符号-homospermidine，精胺，和thermospermine和更长链和支链多胺。还对腐胺进行了生物化学修饰，以用于代谢调节和分解代谢，例如N-乙酰化和N-谷氨酰化，以及掺入专门的代谢产物中，例如N-甲基化，N-柠檬酸化，N-棕榈酰化，N-羟基化和N-羟基肉桂酸化。仅已知一个实例，其中在亚甲基碳上修饰了腐胺：由未知的C-羟化酶形成2-羟基腐胺。在这里，我们报告了以前未描述的腐胺2-羟化酶（一种来自β-变形杆菌支气管博德特氏菌和青枯雷尔氏菌的Rieske型非血红素铁硫蛋白）的功能鉴定。。腐胺2-羟化酶的鉴定将有助于2-羟酪胺的生理功能的研究。2 hydroxyputrescine的一个已知角色有直接的生物医学相关性：其在循环氧肟酸铁载体alcaligin，百日咳，对病原体的潜在毒力因子的生物合成作用，百日咳杆菌。我们还报告了从γ-变形杆菌Shewanella oneidensis，它与FAD和NADPH依赖鸟氨酸和赖氨酸N-单加氧酶参与铁载体生物合成同源的腐胺N-羟化酶的功能鉴定。腐胺N-羟化酶在大肠杆菌中的异源表达产生的游离N-羟基putrescine，以前在生物系统中从未发现过。此外，此处鉴定的腐胺C-和N-羟基酶可以为多胺结构支架贡献新功能，包括合成生物学策略中的CH键功能化。

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Functional Identification of Putrescine C- and N-Hydroxylases

The small polyamine putrescine (1,4-diaminobutane) is ubiquitously and abundantly found in all three domains of life. It is a precursor, through N-aminopropylation or N-aminobutylation, for biosynthesis of the longer polyamines spermidine, sym-homospermidine, spermine, and thermospermine and longer and branched chain polyamines. Putrescine is also biochemically modified for purposes of metabolic regulation and catabolism, e.g.N-acetylation and N-glutamylation, and for incorporation into specialized metabolites, e.g.N-methylation, N-citrylation, N-palmitoylation, N-hydroxylation, and N-hydroxycinnamoylation. Only one example is known where putrescine is modified on a methylene carbon: the formation of 2-hydroxyputrescine by an unknown C-hydroxylase. Here, we report the functional identification of a previously undescribed putrescine 2-hydroxylase, a Rieske-type nonheme iron sulfur protein from the β-proteobacteria Bordetella bronchiseptica and Ralstonia solanacearum. Identification of the putrescine 2-hydroxylase will facilitate investigation of the physiological functions of 2-hydroxyputrescine. One known role of 2-hydroxyputrescine has direct biomedical relevance: its role in the biosynthesis of the cyclic hydroxamate siderophore alcaligin, a potential virulence factor of the causative agent of whooping cough, Bordetella pertussis. We also report the functional identification of a putrescine N-hydroxylase from the γ-proteobacterium Shewanella oneidensis, which is homologous to FAD- and NADPH-dependent ornithine and lysine N-monooxygenases involved in siderophore biosynthesis. Heterologous expression of the putrescine N-hydroxylase in E. coli produced free N-hydroxyputrescine, never detected previously in a biological system. Furthermore, the putrescine C- and N-hydroxylases identified here could contribute new functionality to polyamine structural scaffolds, including C–H bond functionalization in synthetic biology strategies.

更新日期：2016-08-24

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