Targeting the cysteine biosynthesis pathway in microorganisms: Mechanism, structure, and drug discovery,European Journal of Medicinal Chemistry

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Targeting the cysteine biosynthesis pathway in microorganisms: Mechanism, structure, and drug discovery
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2024-04-28 , DOI: 10.1016/j.ejmech.2024.116461
Ying Tao ₁ , Dandan Zheng ₁ , Wei Zou ₁ , Ting Guo ₁ , Guojian Liao ₁ , Wei Zhou ₁

Affiliation

Owing to the global health crisis of resistant pathogenic infections, researchers are emphasizing the importance of novel prevention and control strategies. Existing antimicrobial drugs predominantly target a few pathways, and their widespread use has pervasively increased drug resistance. Therefore, it is imperative to develop new antimicrobial drugs with novel targets and chemical structures. The cysteine biosynthesis pathway, one of the microbial metabolic pathways, plays a crucial role in pathogenicity and drug resistance. This pathway notably differs from that in humans, thereby representing an unexplored target for developing antimicrobial drugs. Herein, we have presented an overview of cysteine biosynthesis pathways and their roles in the pathogenicity of various microorganisms. Additionally, we have investigated the structure and function of enzymes involved in these pathways as well as have discussed drug design strategies and structure–activity relationships of the enzyme inhibitors. This review provides valuable insights for developing novel antimicrobials and offers new avenues to combat drug resistance.

中文翻译：

靶向微生物中的半胱氨酸生物合成途径：机制、结构和药物发现

由于耐药病原体感染的全球健康危机，研究人员强调新的预防和控制策略的重要性。现有的抗菌药物主要针对几种途径，它们的广泛使用普遍增加了耐药性。因此，开发具有新靶点和化学结构的新型抗菌药物势在必行。半胱氨酸生物合成途径是微生物代谢途径之一，在致病性和耐药性中发挥着至关重要的作用。该途径与人类的途径明显不同，因此代表了开发抗菌药物的尚未探索的目标。在此，我们概述了半胱氨酸生物合成途径及其在各种微生物致病性中的作用。此外，我们还研究了这些途径中涉及的酶的结构和功能，并讨论了酶抑制剂的药物设计策略和构效关系。该综述为开发新型抗菌药物提供了宝贵的见解，并提供了对抗耐药性的新途径。

更新日期：2024-04-28

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