Mycobacterium abscessus belongs to a group of rapidly growing mycobacteria (RGM) and accounts for approximately 65–80% of lung disease caused by RGM. It is highly pathogenic and is considered the prominent Mycobacterium involved in pulmonary infection in patients with cystic fibrosis and chronic pulmonary disease (CPD). FosM is a putative 134 amino acid fosfomycin resistance enzyme from M. abscessus subsp. bolletii that shares approximately 30–55% sequence identity with other vicinal oxygen chelate (VOC) fosfomycin resistance enzymes and represents the first of its type found in any Mycobacterium species. Genes encoding VOC fosfomycin resistance enzymes have been found in both Gram-positive and Gram-negative pathogens. Given that FosA enzymes from Gram-negative bacteria have evolved optimum activity towards glutathione (GSH) and FosB enzymes from Gram-positive bacteria have evolved optimum activity towards bacillithiol (BSH), it was originally suggested that FosM might represent a fourth class of enzyme that has evolved to utilize mycothiol (MSH). However, a sequence similarity network (SSN) analysis identifies FosM as a member of the FosX subfamily, indicating that it may utilize water as a substrate. Here we have synthesized MSH and characterized FosM with respect to divalent metal ion activation and nucleophile selectivity. Our results indicate that FosM is a Mn²⁺-dependent FosX-type hydrase with no selectivity toward MSH or other thiols as analyzed by NMR and mass spectroscopy.

中文翻译：

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脓肿分枝杆菌的基因组编码的磷霉素抗性酶的表征。

脓肿分枝杆菌属于一组快速生长的分枝杆菌（RGM），约占RGM引起的肺部疾病的65-80％。它是高致病性的，被认为是囊性纤维化和慢性肺病（CPD）患者参与肺部感染的主要分枝杆菌。FosM是一种来自脓肿分支杆菌的推定的134个氨基酸的磷霉素抗性酶亚种 bolletii与其他邻近的氧螯合（VOC）磷霉素抗性酶具有大约30-55％的序列同一性，并且代表了在任何分枝杆菌物种中发现的首个类型。在革兰氏阳性和革兰氏阴性病原体中都发现了编码VOC磷霉素抗性酶的基因。鉴于革兰氏阴性细菌的FosA酶已对谷胱甘肽（GSH）进化出最佳活性，革兰氏阳性细菌的FosB酶已对乙硫醇（BSH）进化出最佳活性，最初建议FosM可能代表第四类酶，已经进化为利用麦硫酚（MSH）。但是，序列相似性网络（SSN）分析将FosM识别为FosX子家族的成员，表明它可能利用水作为底物。在这里，我们已经合成了MSH并就二价金属离子的活化和亲核试剂的选择性对FosM进行了表征。我们的结果表明，FosM是一种锰通过NMR和质谱分析，对²⁺依赖性的FosX型水合酶对MSH或其他硫醇没有选择性。