Characterization of SfmD as a Heme Peroxidase That Catalyzes the Regioselective Hydroxylation of 3-Methyltyrosine to 3-Hydroxy-5-methyltyrosine in Saframycin A Biosynthesis
文献类型：期刊论文
| 作者 | Tang MC(唐满成) ; Fu CY(付骋宇) ; Tang GL(唐功利) |
| 刊名 | J. Biol. Chem.
 |
| 出版日期 | 2012 |
| 卷号 | 287期号:7页码:5112-5121 |
| ISSN号 | 0021-9258 |
| 其他题名 | 阐明番红霉素A生物合成中SfmD是一个血红素依赖的过氧化酶催化3-甲基酪氨酸到3-羟基-5-甲基酪氨酸的区域选择性羟化 |
| 英文摘要 | Saframycin A (SFM-A) is a potent antitumor antibiotic that belongs to the tetrahydroisoquinoline family. Biosynthetic studies have revealed that its unique pentacyclic core structure is derived from alanine, glycine, and non-proteinogenic amino acid 3-hydroxy-5-methyl-O-methyltyrosine (3-OH-5-Me-OMe-Tyr). SfmD, a hypothetical protein in the biosynthetic pathway of SFM-A, was hypothesized to be responsible for the generation of the 3-hydroxy group of 3-OH-5-Me-OMe-Tyr based on previously heterologous expression results. We now report the in vitro characterization of SfmD as a novel hemecontaining peroxidase that catalyzes the hydroxylation of 3-methyltyrosine to 3-hydroxy-5-methyltyrosine using hydrogen peroxide as the oxidant. In addition, we elucidated the biosynthetic pathway of 3-OH-5-Me-OMe-Tyr by kinetic studies of SfmD in combination with biochemical assays of SfmM2, a methyltransferase within the same pathway. Furthermore, SacD, a counterpart of SfmD involved in safracin B biosynthesis, was also characterized as a heme-containing peroxidase, suggesting that SfmD-like heme-containing peroxidases may be commonly involved in the biosynthesis of SFM-A and its analogs. Finally, we found that the conserved motif HXXXC is crucial for heme binding using comparative UV-Vis and Magnetic Circular Dichroism (MCD) spectra studies of SfmD wild-type and mutants. Together, these findings expand the category of heme-containing peroxidases and set the stage for further mechanistic studies. In addition, this study has critical implications for delineating the biosynthetic pathway of other related tetrahydroisoquinoline family members. |
| 学科主题 | 生命有机化学 |
| 收录类别 | SCI |
| 原文出处 | http://dx.doi.org/10.1074/jbc.M111.306316 |
| 语种 | 英语 |
| WOS记录号 | WOS:000300608500069 |
| 公开日期 | 2013-08-23 |
| 源URL | [http://202.127.28.38/handle/331003/28541]  |
| 专题 | 上海有机化学研究所_生命有机化学国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Tang MC,Fu CY,Tang GL. Characterization of SfmD as a Heme Peroxidase That Catalyzes the Regioselective Hydroxylation of 3-Methyltyrosine to 3-Hydroxy-5-methyltyrosine in Saframycin A Biosynthesis[J]. J. Biol. Chem.,2012,287(7):5112-5121. |
| APA | 唐满成,付骋宇,&唐功利.(2012).Characterization of SfmD as a Heme Peroxidase That Catalyzes the Regioselective Hydroxylation of 3-Methyltyrosine to 3-Hydroxy-5-methyltyrosine in Saframycin A Biosynthesis.J. Biol. Chem.,287(7),5112-5121. |
| MLA | 唐满成,et al."Characterization of SfmD as a Heme Peroxidase That Catalyzes the Regioselective Hydroxylation of 3-Methyltyrosine to 3-Hydroxy-5-methyltyrosine in Saframycin A Biosynthesis".J. Biol. Chem. 287.7(2012):5112-5121. |
入库方式： OAI收割
来源：上海有机化学研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。