Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa 3886, South Africa.
Department of Molecular Microbiology and Genetics, University of Göttingen, 37077 Göttingen, Germany.
Int J Mol Sci. 2023 Feb 19;24(4):4161. doi: 10.3390/ijms24044161.
Cytochrome P450 monooxygenases (CYPs/P450s) and their redox partners, ferredoxins, are ubiquitous in organisms. P450s have been studied in biology for over six decades owing to their distinct catalytic activities, including their role in drug metabolism. Ferredoxins are ancient proteins involved in oxidation-reduction reactions, such as transferring electrons to P450s. The evolution and diversification of P450s in various organisms have received little attention and no information is available for archaea. This study is aimed at addressing this research gap. Genome-wide analysis revealed 1204 P450s belonging to 34 P450 families and 112 P450 subfamilies, where some families and subfamilies are expanded in archaea. We also identified 353 ferredoxins belonging to the four types 2Fe-2S, 3Fe-4S, 7Fe-4S and 2[4Fe-4S] in 40 archaeal species. We found that bacteria and archaea shared the CYP109, CYP147 and CYP197 families, as well as several ferredoxin subtypes, and that these genes are co-present on archaeal plasmids and chromosomes, implying the plasmid-mediated lateral transfer of these genes from bacteria to archaea. The absence of ferredoxins and ferredoxin reductases in the P450 operons suggests that the lateral transfer of these genes is independent. We present different scenarios for the evolution and diversification of P450s and ferredoxins in archaea. Based on the phylogenetic analysis and high affinity to diverged P450s, we propose that archaeal P450s could have diverged from CYP109, CYP147 and CYP197. Based on this study's results, we propose that all archaeal P450s are bacterial in origin and that the original archaea had no P450s.
细胞色素 P450 单加氧酶（CYPs/P450s）及其氧化还原伴侣铁氧还蛋白在生物界中普遍存在。由于其独特的催化活性，包括在药物代谢中的作用，P450s 在生物学领域已经研究了六十多年。铁氧还蛋白是参与氧化还原反应的古老蛋白质，例如将电子转移给 P450s。不同生物中 P450s 的进化和多样化受到的关注较少，而关于古菌的信息则没有。本研究旨在解决这一研究空白。全基因组分析揭示了 1204 种 P450，属于 34 个 P450 家族和 112 个 P450 亚家族，其中一些家族和亚家族在古菌中扩张。我们还在 40 种古菌中鉴定了 353 种铁氧还蛋白，属于 2Fe-2S、3Fe-4S、7Fe-4S 和 2[4Fe-4S]四种类型。我们发现细菌和古菌共享 CYP109、CYP147 和 CYP197 家族以及几种铁氧还蛋白亚型，这些基因共同存在于古菌质粒和染色体上，这意味着这些基因通过质粒从细菌侧向转移到古菌中。P450 操纵子中缺乏铁氧还蛋白和铁氧还蛋白还原酶表明这些基因的侧向转移是独立的。我们提出了不同的情景来解释古菌中 P450s 和铁氧还蛋白的进化和多样化。基于系统发育分析和对分化的 P450s 的高亲和力，我们提出古菌 P450s 可能从 CYP109、CYP147 和 CYP197 分化而来。基于本研究的结果，我们提出所有古菌 P450s 均来自细菌，原始古菌没有 P450s。
