Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
IUBMB Life. 2021 Apr;73(4):643-658. doi: 10.1002/iub.2455. Epub 2021 Mar 5.
Tuberculosis caused by the bacterium, Mycobacterium tuberculosis (Mtb), continues to remain one of the most devastating infectious diseases afflicting humans. Although there are several drugs for treating tuberculosis available currently, the emergence of the drug resistant forms of this pathogen has made its treatment and eradication a challenging task. While the replication machinery, protein synthesis and cell wall biogenesis of Mtb have been targeted often for anti-tubercular drug development a number of essential metabolic pathways crucial to its survival have received relatively less attention. In this context a number of amino acid biosynthesis pathways have recently been shown to be essential for the survival and pathogenesis of Mtb. Many of these pathways and or their key enzymes homologs are absent in humans hence they could be harnessed for anti-tubercular drug development. In this review, we describe comprehensively the amino acid metabolic pathways essential in Mtb and the key enzymes involved therein that are being investigated for developing inhibitors that compromise the survival and pathogenesis caused by this pathogen.
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）引起的结核病仍然是对人类危害最大的传染病之一。虽然目前有几种治疗结核病的药物，但这种病原体耐药形式的出现使得治疗和消除它成为一项具有挑战性的任务。尽管 Mtb 的复制机制、蛋白质合成和细胞壁生物发生经常成为抗结核药物开发的目标，但许多对其生存至关重要的关键代谢途径相对较少受到关注。在这种情况下，最近已经证明许多氨基酸生物合成途径对于 Mtb 的生存和发病机制是必需的。这些途径中的许多途径或其关键酶同源物在人类中不存在，因此它们可以被用于开发抗结核药物。在这篇综述中，我们全面描述了 Mtb 中必需的氨基酸代谢途径以及涉及其中的关键酶，这些酶正在被研究用于开发抑制剂，以破坏这种病原体引起的生存和发病机制。
