Ras Tertius Alwyn, Strauss Erick, Botes Annelise
Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
Front Microbiol. 2021 Dec 20;12:791756. doi: 10.3389/fmicb.2021.791756. eCollection 2021.
are responsible for a wide range of disease states in both humans and animals, in which their parasitic lifestyle has allowed them to reduce their genome sizes and curtail their biosynthetic capabilities. The subsequent dependence on their host offers a unique opportunity to explore pathways for obtaining and producing cofactors - such as coenzyme A (CoA) - as possible targets for the development of new anti-mycoplasma agents. CoA plays an essential role in energy and fatty acid metabolism and is required for membrane synthesis. However, our current lack of knowledge of the relevance and importance of the CoA biosynthesis pathway in mycoplasmas, and whether it could be bypassed within their pathogenic context, prevents further exploration of the potential of this pathway. In the universal, canonical CoA biosynthesis pathway, five enzymes are responsible for the production of CoA. Given the inconsistent presence of the genes that code for these enzymes across genomes, this study set out to establish the genetic capacity of mycoplasmas to synthesize their own CoA . Existing functional annotations and sequence, family, motif, and domain analysis of protein products were used to determine the existence of relevant genes in genomes. We found that most species do have the genetic capacity to synthesize CoA, but there was a differentiated prevalence of these genes across species. Phylogenetic analysis indicated that the phylogenetic position of a species could not be used to predict its enzyme-encoding gene combinations. Despite this, the final enzyme in the biosynthesis pathway - dephospho-coenzyme A kinase (DPCK) - was found to be the most common among the studied species, suggesting that it has the most potential as a target in the search for new broad-spectrum anti-mycoplasma agents.
支原体在人类和动物中会引发多种疾病状态，其寄生生活方式使其基因组大小减小，生物合成能力受限。随后对宿主的依赖为探索获取和产生辅酶等辅因子的途径提供了独特机会，例如辅酶A（CoA），可将其作为开发新型抗支原体药物的潜在靶点。CoA在能量和脂肪酸代谢中起关键作用，是膜合成所必需的。然而，我们目前对支原体中CoA生物合成途径的相关性和重要性缺乏了解，以及在其致病环境中该途径是否可以被绕过，这阻碍了对该途径潜力的进一步探索。在通用的经典CoA生物合成途径中，五种酶负责CoA的产生。鉴于编码这些酶的基因在不同基因组中的存在情况不一致，本研究旨在确定支原体合成自身CoA的遗传能力。利用现有的功能注释以及蛋白质产物的序列、家族、基序和结构域分析来确定基因组中相关基因的存在。我们发现大多数支原体物种确实具有合成CoA的遗传能力，但这些基因在不同物种中的流行程度存在差异。系统发育分析表明，一个物种的系统发育位置不能用于预测其酶编码基因组合。尽管如此，生物合成途径中的最后一种酶——脱磷酸辅酶A激酶（DPCK）——在研究的物种中是最常见的，这表明它在寻找新型广谱抗支原体药物方面最具作为靶点的潜力。
