Gutensohn Mareike, Schaefer Jeffra K, Maas Torben J, Skyllberg Ulf, Björn Erik
Department of Chemistry, Umeå University, Umeå, Sweden.
Department of Environmental Sciences, Rutgers University, New Brunswick, NJ, United States.
Front Microbiol. 2023 Jan 11;13:1085214. doi: 10.3389/fmicb.2022.1085214. eCollection 2022.
Low-molecular-mass (LMM) thiol compounds are known to be important for many biological processes in various organisms but LMM thiols are understudied in anaerobic bacteria. In this work, we examined the production and turnover of nanomolar concentrations of LMM thiols with a chemical structure related to cysteine by the model iron-reducing bacterium . Our results show that tightly controls the production, excretion and intracellular concentration of thiols depending on cellular growth state and external conditions. The production and cellular export of endogenous cysteine was coupled to the extracellular supply of Fe(II), suggesting that cysteine excretion may play a role in cellular trafficking to iron proteins. Addition of excess exogenous cysteine resulted in a rapid and extensive conversion of cysteine to penicillamine by the cells. Experiments with added isotopically labeled cysteine confirmed that penicillamine was formed by a dimethylation of the C-3 atom of cysteine and not indirect metabolic responses to cysteine exposure. This is the first report of metabolic synthesis of this compound. Penicillamine formation increased with external exposure to cysteine but the compound did not accumulate intracellularly, which may suggest that it is part of ' metabolic strategy to maintain cysteine homeostasis. Our findings highlight and expand on processes mediating homeostasis of cysteine-like LMM thiols in strict anaerobic bacteria. The formation of penicillamine is particularly noteworthy and this compound warrants more attention in microbial metabolism studies.
低分子量（LMM）硫醇化合物已知对各种生物体中的许多生物过程很重要，但LMM硫醇在厌氧细菌中研究较少。在这项工作中，我们通过模型铁还原细菌研究了与半胱氨酸化学结构相关的纳摩尔浓度LMM硫醇的产生和周转。我们的结果表明， 根据细胞生长状态和外部条件严格控制硫醇的产生、排泄和细胞内浓度。内源性半胱氨酸的产生和细胞输出与细胞外Fe（II）的供应相关，这表明半胱氨酸排泄可能在细胞向铁蛋白的运输中起作用。添加过量的外源性半胱氨酸导致细胞将半胱氨酸快速广泛地转化为青霉胺。添加同位素标记的半胱氨酸的实验证实，青霉胺是由半胱氨酸的C-3原子二甲基化形成的，而不是对半胱氨酸暴露的间接代谢反应。这是该化合物代谢合成的首次报道。青霉胺的形成随着外部对半胱氨酸的暴露而增加，但该化合物没有在细胞内积累，这可能表明它是维持半胱氨酸稳态的“代谢策略”的一部分。我们的发现突出并扩展了严格厌氧细菌中介导类半胱氨酸LMM硫醇稳态的过程。青霉胺的形成特别值得注意，这种化合物在微生物代谢研究中值得更多关注。
