Tuberculosis (TB) is a devastating and rapidly spreading disease caused by Mycobacterium tuberculosis (Mtb). Therapy requires prolonged treatment with a combination of multiple agents and interruptions in the treatment regimen result in emergence and spread of multi-drug resistant (MDR) Mtb strains. MDR Mtb poses a significant global health problem, calling for urgent development of novel drugs to combat TB. Here, we report the 3.3 Å resolution structure of the ~2 MDa type-I fatty acid synthase (FAS-I) from Mtb, determined by single particle cryo-EM. Mtb FAS-I is an essential enzymatic complex that contributes to the virulence of Mtb, and thus a prime target for anti-TB drugs. The structural information for Mtb FAS-I we have obtained enables computer-based drug discovery approaches, and the resolution achieved by cryo-EM is sufficient for elucidating inhibition mechanisms by putative small molecular weight inhibitors.

中文翻译：

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I型结核分枝杆菌脂肪酸合酶的结构，分辨率为3.3Å。

结核病（TB）是一种由结核分枝杆菌（Mtb）引起的破坏性且迅速扩散的疾病。治疗需要长时间使用多种药物联合治疗，治疗方案中的中断会导致多药耐药（MDR）Mtb菌株的出现和传播。耐多药结核病引起了全球性的重大健康问题，呼吁紧急开发新型药物来抗击结核病。在这里，我们报道了由Mtb产生的〜2 MDa I型脂肪酸合酶（FAS-I）的3.3Å分辨率结构，该结构由单粒子冷冻电磁法测定。Mtb FAS-1是必不可少的酶复合物，有助于Mtb的毒性，因此是抗结核药物的主要靶标。我们获得的Mtb FAS-I的结构信息可用于基于计算机的药物发现方法，