Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences, 75007, Uppsala, Sweden.
Microb Ecol. 2024 Nov 15;87(1):141. doi: 10.1007/s00248-024-02458-0.
The single-step methioninase-mediated degradation of methionine (as a sulfur containing amino acid) is a reaction at the interface of carbon, nitrogen, sulfur, and methane metabolism in microbes. This enzyme also has therapeutic application due to its role in starving auxotrophic cancer cells. Applying our refined in silico screening pipeline on 33,469 publicly available genome assemblies and 1878 metagenome assembled genomes/single-cell amplified genomes from brackish waters of the Caspian Sea and the Fennoscandian Shield deep groundwater resulted in recovering 1845 methioninases. The majority of recovered methioninases belong to representatives of phyla Proteobacteria (50%), Firmicutes (29%), and Firmicutes_A (13%). Prevalence of methioninase among anaerobic microbes and in the anoxic deep groundwater together with the relevance of its products for energy conservation in anaerobic metabolism highlights such environments as desirable targets for screening novel methioninases and resolving its contribution to microbial metabolism and interactions. Among archaea, majority of detected methioninases are from representatives of Methanosarcina that are able to use methanethiol, the sulfur containing product from methionine degradation, as a precursor for methanogenesis. Branching just outside these archaeal methioninases in the phylogenetic tree, we recovered three methioninases belonging to representatives of Patescibacteria reconstructed from deep groundwater metagenomes. We hypothesize that methioninase in Patescibacteria could contribute to their syntrophic interactions where their methanogenic partners/hosts benefit from the produced 2-oxobutyrate and methanethiol. Our results underscore the significance of accounting for specific ecological niche in screening for enzyme variates with desired characteristics. Finally, complementing of our findings with experimental validation of methioninase activity confirms the potential of our in silico screening in clarifying the peculiar ecological role of methioninase in anoxic environments.
一步法甲硫氨酸酶介导的甲硫氨酸（作为含硫氨基酸）降解是微生物中碳、氮、硫和甲烷代谢界面的反应。由于其在饿死营养缺陷型癌细胞中的作用，该酶也具有治疗应用。我们在 33469 个公开的基因组组装和 1878 个咸海和芬诺斯堪的亚盾深地下水的宏基因组组装基因组/单细胞扩增基因组中应用我们改进的计算筛选管道，结果恢复了 1845 种甲硫氨酸酶。回收的甲硫氨酸酶大多数属于变形菌门（Proteobacteria）（50%）、厚壁菌门（Firmicutes）（29%）和Firmicutes_A（13%）的代表。甲硫氨酸酶在厌氧微生物和缺氧深地下水中的普遍性以及其产物在厌氧代谢中对能量保存的重要性，突出了这些环境是筛选新型甲硫氨酸酶的理想目标，并解决了其对微生物代谢和相互作用的贡献。在古菌中，大多数检测到的甲硫氨酸酶来自 Methanosarcina 的代表，它们能够使用甲硫醇，即甲硫氨酸降解的含硫产物，作为甲烷生成的前体。在系统发育树中，这些古菌甲硫氨酸酶的分支之外，我们从深地下水宏基因组中恢复了属于 Patescibacteria 的三个甲硫氨酸酶。我们假设 Patescibacteria 中的甲硫氨酸酶可能有助于它们的共生相互作用，其中它们的产甲烷伙伴/宿主受益于产生的 2-氧代丁酸和甲硫醇。我们的结果强调了在筛选具有所需特征的酶变体时考虑特定生态位的重要性。最后，通过实验验证甲硫氨酸酶活性补充我们的发现，证实了我们在阐明缺氧环境中甲硫氨酸酶特殊生态作用的计算筛选的潜力。
