Biochemical characterisation of methanethiol oxidase: a key enzyme of volatile organosulfur compound degradation

甲硫醇氧化酶的生化表征：挥发性有机硫化合物降解的关键酶

• 批准号: BB/H003851/1
• 负责人: Hendrik Schaefer
• 金额: $ 44.52万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH003851%2F1
• 关键词: Biochemical; characterisation; methanethiol; oxidase; key

We propose to characterise the properties of a bacterial enzyme that converts a foul smelling, toxic gaseous organic sulfur compound. Methanethiol oxidase converts methanethiol - a gas smelling of rotten cabbage - which is an important sulfur compound in nature. The products of the methanethiol catalysed reaction are formaldehyde, hydrogen sulfide (smells of rotten eggs) and hydrogen peroxide (a chemical that is used as a bleaching agent in contact lens disinfection fluids). Very little is known of the molecular and catalytic properties of methanethiol oxidases. The work we propose will provide fundamental insights into the biochemistry of methanethiol degradation, a process that on a global scale is responsible for turnover of some 300-500 million tons of sulfur in the oceans alone, where methanethiol occurs as a degradation product of a climate cooling gas (dimethylsulfide) and its precursor molecule (dimethylsulfoniopropionate). Methanethiol plays a role as a flavour compound in foods and beverages, but can also contribute to what we perceive as off-flavours when it occurs at too high concentrations. In an industrial context, methanethiol is also significant as a degradation product of bulk solvents (dimethylsulfoxide) and it is conceivable that methanethiol oxidase could find application as an industrial biocatalyst. Our preliminary data also indicate that this enzyme may work in concert with other enzymes in a complex of proteins inside the cell, which may protect it to some degree from its toxic intermediates and may enhance its function. This enzyme complex will also be studied further. An interesting aspect of methanethiol oxidase that we have just discovered is that this bacterial enzyme is encoded by a gene for which there has not been any information indicating its function previously. It is hence of interest to further investigate the enzyme, in particular as there are similar enzymes encoded by genomes of animals including humans on whose function similarly little is known. Thus, studying this bacterial enzyme in more detail, may shed light on the evolution of a type of protein which is also found in our bodies. The ultimate goal of characterising an enzyme is to elucidate its three dimensional structure. While this is not planned in this project, we aim to make the first step towards achieving that goal by producing crystals of the enzyme that can be characterised by X-ray diffraction analysis. This will require using recombinant DNA technology, which will allow to produce sufficient amounts of the enzyme for crystallisation.

我们建议表征一种细菌酶的特性，该酶可转化恶臭、有毒的气态有机硫化合物。甲硫醇氧化酶可转化甲硫醇（一种具有腐烂卷心菜气味的气体），而甲硫醇是自然界中一种重要的硫化合物。甲硫醇催化反应的产物是甲醛、硫化氢（有臭鸡蛋味）和过氧化氢（一种在隐形眼镜消毒液中用作漂白剂的化学物质）。人们对甲硫醇氧化酶的分子和催化特性知之甚少。我们提出的工作将为甲硫醇降解的生物化学提供基本见解，这一过程在全球范围内导致仅海洋中约 300-5 亿吨硫的周转，其中甲硫醇作为气候的降解产物而存在冷却气体（二甲基硫醚）及其前体分子（二甲基磺基丙酸酯）。甲硫醇在食品和饮料中起着风味化合物的作用，但当它浓度过高时，也会导致我们认为的异味。在工业背景下，甲硫醇作为大量溶剂（二甲基亚砜）的降解产物也很重要，并且可以想象甲硫醇氧化酶可以作为工业生物催化剂得到应用。我们的初步数据还表明，这种酶可能与细胞内蛋白质复合物中的其他酶协同工作，这可以在一定程度上保护细胞免受有毒中间体的影响，并可以增强其功能。这种酶复合物也将得到进一步研究。我们刚刚发现的甲硫醇氧化酶的一个有趣的方面是，这种细菌酶是由一个基因编码的，之前没有任何信息表明其功能。因此，进一步研究这种酶是很有意义的，特别是因为包括人类在内的动物基因组编码了类似的酶，其功能同样知之甚少。因此，更详细地研究这种细菌酶可能有助于揭示我们体内也存在的一种蛋白质的进化。表征酶的最终目标是阐明其三维结构。虽然本项目没有计划这样做，但我们的目标是通过生产可通过 X 射线衍射分析表征的酶晶体，为实现这一目标迈出第一步。这将需要使用重组 DNA 技术，该技术将能够产生足够量的用于结晶的酶。

项目成果

Bacterial SBP56 identified as a Cu-dependent methanethiol oxidase widely distributed in the biosphere.

• DOI: 10.1038/ismej.2017.148
• 发表时间: 2018-01
• 期刊: The ISME journal
• 作者: Eyice Ö;Myronova N;Pol A;Carrión O;Todd JD;Smith TJ;Gurman SJ;Cuthbertson A;Mazard S;Mennink-Kersten MA;Bugg TD;Andersson KK;Johnston AW;Op den Camp HJ;Schäfer H
• 通讯作者: Schäfer H

Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis.

• DOI: 10.1038/s41588-017-0006-7
• 发表时间: 2018-01
• 期刊: Nature genetics
• 影响因子: 30.8
• 作者: Pol A;Renkema GH;Tangerman A;Winkel EG;Engelke UF;de Brouwer APM;Lloyd KC;Araiza RS;van den Heuvel L;Omran H;Olbrich H;Oude Elberink M;Gilissen C;Rodenburg RJ;Sass JO;Schwab KO;Schäfer H;Venselaar H;Sequeira JS;Op den Camp HJM;Wevers RA
• 通讯作者: Wevers RA