双环分子
化学
生物合成
立体化学
化学合成
化学生物学
吲哚试验
组合化学
酶
生物化学
体外
作者
Xinhui Li,Suze Ma,Qi Zhang
标识
DOI:10.1016/j.tetlet.2023.154337
摘要
Antibiotic resistance is a huge public health security crisis around the world. Darobactin is a ribosomally produced and post-translationally modified heptapeptide antibiotic with a unique bicyclic structure. This compound is highly effective against a variety of Gram-negative pathogens by targeting the outer membrane protein BamA. The biosynthetic pathway of darobactin involves a highly versatile radical S-adenosylmethionine (SAM) enzyme DarE, which is responsible for the formation of the unique indole-based bicyclic cyclophane structure. Recently, total synthesis of darobactin was achieved independently by different research groups, utilizing Larock heteroannulation as a key step to construct the bicyclic structure. This paper reviews the recent studies in the chemistry and biology of darobactin, including biosynthetic pathway, chemical synthesis, antibacterial mode of action, and bioengineering studies.
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