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学科主题: 生命有机化学
题名: Characterization of SfmD as a Heme Peroxidase That Catalyzes the Regioselective Hydroxylation of 3-Methyltyrosine to 3-Hydroxy-5-methyltyrosine in Saframycin A Biosynthesis
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
作者: Tang MC(唐满成) ; Fu CY(付骋宇) ; Tang GL(唐功利)
刊名: J. Biol. Chem.
发表日期: 2012
卷: 287, 期:7, 页:5112-5121
收录类别: SCI
部门归属: 中科院上海有机化学研究所
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.
语种: 英语
相关网址: 查看原文
WOS记录号: WOS:000300608500069
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/28541
Appears in Collections:生命有机化学国家重点实验室_期刊论文

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Recommended Citation:
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.
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