Cooley Richard B, Dubbels Bradley L, Sayavedra-Soto Luis A, Bottomley Peter J, Arp Daniel J
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
Department of Botany and Plant Pathology, Oregon State University, Corvallis, OR 97331, USA.
Microbiology (Reading). 2009 Jun;155(Pt 6):2086-2096. doi: 10.1099/mic.0.028175-0. Epub 2009 Apr 21.
Soluble butane monooxygenase (sBMO), a three-component di-iron monooxygenase complex expressed by the C(2)-C(9) alkane-utilizing bacterium Thauera butanivorans, was kinetically characterized by measuring substrate specificities for C(1)-C(5) alkanes and product inhibition profiles. sBMO has high sequence homology with soluble methane monooxygenase (sMMO) and shares a similar substrate range, including gaseous and liquid alkanes, aromatics, alkenes and halogenated xenobiotics. Results indicated that butane was the preferred substrate (defined by k(cat) : K(m) ratios). Relative rates of oxidation for C(1)-C(5) alkanes differed minimally, implying that substrate specificity is heavily influenced by differences in substrate K(m) values. The low micromolar K(m) for linear C(2)-C(5) alkanes and the millimolar K(m) for methane demonstrate that sBMO is two to three orders of magnitude more specific for physiologically relevant substrates of T. butanivorans. Methanol, the product of methane oxidation and also a substrate itself, was found to have similar K(m) and k(cat) values to those of methane. This inability to kinetically discriminate between the C(1) alkane and C(1) alcohol is observed as a steady-state concentration of methanol during the two-step oxidation of methane to formaldehyde by sBMO. Unlike methanol, alcohols with chain length C(2)-C(5) do not compete effectively with their respective alkane substrates. Results from product inhibition experiments suggest that the geometry of the active site is optimized for linear molecules four to five carbons in length and is influenced by the regulatory protein component B (butane monooxygenase regulatory component; BMOB). The data suggest that alkane oxidation by sBMO is highly specialized for the turnover of C(3)-C(5) alkanes and the release of their respective alcohol products. Additionally, sBMO is particularly efficient at preventing methane oxidation during growth on linear alkanes > or =C(2,) despite its high sequence homology with sMMO. These results represent, to the best of our knowledge, the first kinetic in vitro characterization of the closest known homologue of sMMO.
可溶性丁烷单加氧酶(sBMO)是一种由利用C(2)-C(9)烷烃的细菌Thauera butanivorans表达的三组分二铁单加氧酶复合物,通过测量其对C(1)-C(5)烷烃的底物特异性和产物抑制谱对其进行了动力学表征。sBMO与可溶性甲烷单加氧酶(sMMO)具有高度的序列同源性,并且具有相似的底物范围,包括气态和液态烷烃、芳烃、烯烃和卤代外源性物质。结果表明丁烷是首选底物(由k(cat):K(m)比值确定)。C(1)-C(5)烷烃的相对氧化速率差异极小,这意味着底物特异性受底物K(m)值差异的严重影响。线性C(2)-C(5)烷烃的低微摩尔K(m)值和甲烷的毫摩尔K(m)值表明,sBMO对Thauera butanivorans的生理相关底物的特异性要高两到三个数量级。甲醇是甲烷氧化的产物,本身也是一种底物,其K(m)值和k(cat)值与甲烷相似。在sBMO将甲烷两步氧化为甲醛的过程中,观察到在稳态甲醇浓度下,无法在动力学上区分C(1)烷烃和C(1)醇。与甲醇不同,链长为C(2)-C(5)的醇不能与其各自的烷烃底物有效竞争。产物抑制实验结果表明,活性位点的几何结构针对长度为四到五个碳的线性分子进行了优化,并且受调节蛋白组分B(丁烷单加氧酶调节组分;BMOB)的影响。数据表明,sBMO对烷烃的氧化高度专门用于C(3)-C(5)烷烃的周转及其各自醇产物的释放。此外,尽管sBMO与sMMO具有高度的序列同源性,但在以≥C(2)的线性烷烃为生长底物时,sBMO在防止甲烷氧化方面特别有效。据我们所知,这些结果代表了对已知最接近sMMO同源物的首次体外动力学表征。