Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Graduate Program in Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, USA.
mSphere. 2019 Jul 10;4(4):e00235-19. doi: 10.1128/mSphere.00235-19.
The virulence of the human pathogen is supported by many heme-dependent proteins, including key enzymes of cellular respiration. Therefore, synthesis of heme is a critical component of staphylococcal physiology. generates heme via the coproporphyrin-dependent pathway, conserved across members of the and In this work, we genetically investigate the oxidation of coproporphyrinogen to coproporphyrin in this heme synthesis pathway. The coproporphyrinogen III oxidase CgoX has previously been identified as the oxygen-dependent enzyme responsible for this conversion under aerobic conditions. However, because uses heme during anaerobic nitrate respiration, we hypothesized that coproporphyrin production is able to proceed in the absence of oxygen. Therefore, we tested the contribution to anaerobic heme synthesis of CgoX and two other proteins previously identified as potential oxygen-independent coproporphyrinogen dehydrogenases, NWMN_1486 and NWMN_1636. We have found that CgoX alone is responsible for aerobic and anaerobic coproporphyrin synthesis from coproporphyrinogen and is required for aerobic and anaerobic heme-dependent growth. This work provides an explanation for how heme synthesis proceeds under both aerobic and anaerobic conditions. Heme is a critical molecule required for aerobic and anaerobic respiration by organisms across kingdoms. The human pathogen has served as a model organism for the study of heme synthesis and heme-dependent physiology and, like many species of the phyla and , generates heme through a coproporphyrin intermediate. A critical step in terminal heme synthesis is the production of coproporphyrin by the CgoX enzyme, which was presumed to be oxygen dependent. However, also requires heme during anaerobic growth; therefore, the synthesis of coproporphyrin by an oxygen-independent mechanism is required. Here, we identify CgoX as the enzyme performing the oxygen-dependent and -independent synthesis of coproporphyrin from coproporphyrinogen, resolving a key outstanding question in the coproporphyrin-dependent heme synthesis pathway.
人类病原体的毒力得到许多血红素依赖蛋白的支持，包括细胞呼吸的关键酶。因此，血红素的合成是葡萄球菌生理的关键组成部分。 通过粪卟啉原依赖性途径生成血红素，该途径在 和 成员中保守。在这项工作中，我们通过遗传方法研究了这个血红素合成途径中粪卟啉原到粪卟啉的氧化。先前已经鉴定出粪卟啉原 III 氧化酶 CgoX 是有氧条件下负责这种转化的氧依赖性酶。然而，由于 在厌氧硝酸盐呼吸过程中使用血红素，我们假设在没有氧气的情况下可以进行粪卟啉的产生。因此，我们测试了 CgoX 以及先前鉴定为潜在氧非依赖性粪卟啉原脱氢酶的两种其他蛋白质 NWMN_1486 和 NWMN_1636 对厌氧血红素合成的贡献。我们发现，CgoX 单独负责粪卟啉原生成有氧和厌氧粪卟啉，并需要有氧和厌氧血红素依赖生长。这项工作解释了 如何在有氧和厌氧条件下进行血红素合成。血红素是所有生物界有氧和无氧呼吸所必需的关键分子。人类病原体 已成为血红素合成和血红素依赖生理研究的模型生物，与许多 和 门的物种一样，通过粪卟啉中间产物生成血红素。末端血红素合成的关键步骤是 CgoX 酶产生粪卟啉，该酶被认为是依赖氧的。然而， 在厌氧生长过程中也需要血红素；因此，需要一种依赖氧的机制来合成粪卟啉。在这里，我们确定 CgoX 是酶，它执行粪卟啉原到粪卟啉的氧依赖和非依赖合成，解决了粪卟啉原依赖性血红素合成途径中的一个关键问题。
