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.

我们建议表征细菌酶的特性，该酶转化了臭味的有毒气态有机有机硫化合物。甲烷硫醇氧化酶转化甲烷硫醇 - 一种烂菜的气味 - 这是一种重要的硫化合物。甲烷硫醇催化反应的产物是甲醛，硫化氢（腐烂的鸡蛋的气味）和过氧化氢（一种用作隐形眼镜消毒液中的漂白剂）。甲烷硫醇氧化酶的分子和催化特性知之甚少。我们提出的工作将提供对甲烷硫醇降解生物化学的基本见解，在全球范围内，仅在海洋中，甲烷硫醇就会导致大约3亿吨的硫酸盐，在那里甲烷硫醇作为气候冷却气（Dimethylsulfide）的降解产物（Dimethylsulfide）及其dimeth-nyl Soleculsy（Dimeth sylsylsylsy）。甲烷硫醇在食品和饮料中扮演着一种风味，但也可以在过高的浓度以过高的浓度时将其视为非燃料。在工业背景下，甲烷硫醇作为散装溶剂（二甲基硫氧化物）的降解产物也很重要，并且可以想象的是，甲烷硫醇氧化酶可以找到作为工业生物催化剂的应用。我们的初步数据还表明，该酶可能与细胞内部蛋白质复合物中的其他酶一起起作用，这可能在某种程度上保护其免受其有毒中间体的影响，并可能增强其功能。该酶复合物也将进一步研究。我们刚刚发现的甲烷硫醇氧化酶的一个有趣的方面是，这种细菌酶是由没有任何信息以前表明其功能的基因编码的。因此，进一步研究该酶是引起关注的，特别是因为有类似的酶由动物的基因组编码，包括人类的功能，其功能几乎没有知名度。因此，更详细地研究这种细菌酶，可能会阐明我们体内也发现的一种蛋白质的演变。表征酶的最终目标是阐明其三维结构。尽管在这个项目中没有计划这一点，但我们旨在通过产生可以通过X射线衍射分析来表征的酶晶体迈出实现该目标的第一步。这将需要使用重组DNA技术，这将允许产生足够量的酶进行结晶。

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