Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain.
Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, Zaragoza, Spain.
Microbiol Spectr. 2022 Apr 27;10(2):e0229421. doi: 10.1128/spectrum.02294-21. Epub 2022 Mar 22.
Flavoproteins are a diverse class of proteins that are mostly enzymes and contain as cofactors flavin mononucleotide (FMN) and/or flavin adenine dinucleotide (FAD), which enable them to participate in a wide range of physiological reactions. We have compiled 78 potential proteins building the flavoproteome of Brucella ovis (B. ovis), the causative agent of ovine brucellosis. The curated list of flavoproteins here reported is based on (i) the analysis of sequence, structure and function of homologous proteins, and their classification according to their structural domains, clans, and expected enzymatic functions; (ii) the constructed phylogenetic trees of enzyme functional classes using 19 Brucella strains and 26 pathogenic and/or biotechnological relevant alphaproteobacteria together with B. ovis; and (iii) the evaluation of the genetic context for each entry. Candidates account for ∼2.7% of the B. ovis proteome, and 75% of them use FAD as cofactor. Only 55% of these flavoproteins belong to the core proteome of Brucella and contribute to B. ovis processes involved in maintenance activities, survival and response to stress, virulence, and/or infectivity. Several of the predicted flavoproteins are highly divergent in Brucella genus from revised proteins and for them it is difficult to envisage a clear function. This might indicate modified catalytic activities or even divergent processes and mechanisms still not identified. We have also detected the lack of some functional flavoenzymes in B. ovis, which might contribute to it being nonzoonotic. Finally, potentiality of B. ovis flavoproteome as the source of antimicrobial targets or biocatalyst is discussed. Some microorganisms depend heavily on flavin-dependent activities, but others maintain them at a minimum. Knowledge about flavoprotein content and functions in different microorganisms will help to identify their metabolic requirements, as well as to benefit either industry or health. Currently, most flavoproteins from the sheep pathogen Brucella ovis are only automatically annotated in databases, and only two have been experimentally studied. Indeed, certain homologues with unknown function are not characterized, and they might relate to still not identified mechanisms or processes. Our research has identified 78 members that comprise its flavoproteome, 76 of them flavoenzymes, which mainly relate to bacteria survival, virulence, and/or infectivity. The list of flavoproteins here presented allows us to better understand the peculiarities of Brucella ovis and can be applied as a tool to search for candidates as new biocatalyst or antimicrobial targets.
黄素蛋白是一大类蛋白质，大多数是酶，含有黄素单核苷酸 (FMN) 和/或黄素腺嘌呤二核苷酸 (FAD) 作为辅因子，使它们能够参与广泛的生理反应。我们已经编译了 78 种潜在的蛋白质，构建了绵羊布鲁氏菌 (B. ovis) 的黄素蛋白组，绵羊布鲁氏菌是绵羊布鲁氏菌病的病原体。这里报告的经过精心整理的黄素蛋白清单基于：(i) 同源蛋白的序列、结构和功能分析，以及根据其结构域、家族和预期的酶功能对它们进行分类；(ii) 使用 19 株布鲁氏菌和 26 株致病和/或生物技术相关的α变形菌以及 B. ovis 构建的酶功能类别的系统发育树；(iii) 对每个条目进行遗传背景评估。候选蛋白占 B. ovis 蛋白质组的约 2.7%，其中 75%使用 FAD 作为辅因子。这些黄素蛋白中只有 55%属于布鲁氏菌的核心蛋白质组，有助于涉及维持活动、生存和应激反应、毒力和/或感染性的 B. ovis 过程。预测的一些黄素蛋白在布鲁氏菌属中与经过修订的蛋白质高度不同，对于它们来说，很难设想一个明确的功能。这可能表明催化活性发生了改变，甚至是尚未确定的不同过程和机制。我们还在 B. ovis 中检测到一些功能性黄素酶的缺失，这可能导致其非动物源性。最后，讨论了 B. ovis 黄素蛋白组作为抗菌靶标或生物催化剂的潜力。一些微生物严重依赖黄素依赖性活性，但其他微生物则将其维持在最低水平。了解不同微生物中黄素蛋白的含量和功能将有助于确定它们的代谢需求，从而有益于工业或健康。目前，绵羊病原体布鲁氏菌 ovis 的大多数黄素蛋白仅在数据库中自动注释，只有两种已进行实验研究。事实上，某些具有未知功能的同源物尚未得到表征，它们可能与尚未确定的机制或过程有关。我们的研究确定了 78 种组成其黄素蛋白组的成员，其中 76 种是黄素酶，主要与细菌的生存、毒力和/或感染性有关。这里呈现的黄素蛋白清单使我们能够更好地了解绵羊布鲁氏菌的特点，并可作为寻找新的生物催化剂或抗菌靶标的工具。
