Alexander M Soohoo, D. Cogan, Krystal L Brodsky, C. Khosla
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引用次数: 0
摘要
三十年来对多功能 6-脱氧赤藓醇内酯 B 合成酶的研究,为了解多酮内酯抗生素生物合成的化学和进化奠定了基础。最近,在将化学和结构生物学工具应用于这种原型装配线聚酮内酯合成酶(PKS)和相关系统方面取得了进展,突显了其催化循环和相关蛋白质动态的一些特征。有令人信服的证据表明,在这个酶家族中已经演化出多种机制,可以沿着由 10-100 个活性位点组成的独特定义序列引导生长的多酮苷链,而每个活性位点在组装线式多酮苷合成酶的整个催化循环中只使用一次。展望未来,我们对重复性克来森类反应自由能的利用机制的理解有望取得重大进展,从而引导不断生长的多酮苷链沿着装配线以一种动力学上稳健、进化上适应性强的方式前进。
Structure and Mechanisms of Assembly-Line Polyketide Synthases.
Three decades of studies on the multifunctional 6-deoxyerythronolide B synthase have laid a foundation for understanding the chemistry and evolution of polyketide antibiotic biosynthesis by a large family of versatile enzymatic assembly lines. Recent progress in applying chemical and structural biology tools to this prototypical assembly-line polyketide synthase (PKS) and related systems has highlighted several features of their catalytic cycles and associated protein dynamics. There is compelling evidence that multiple mechanisms have evolved in this enzyme family to channel growing polyketide chains along uniquely defined sequences of 10-100 active sites, each of which is used only once in the overall catalytic cycle of an assembly-line PKS. Looking forward, one anticipates major advances in our understanding of the mechanisms by which the free energy of a repetitive Claisen-like reaction is harnessed to guide the growing polyketide chain along the assembly line in a manner that is kinetically robust yet evolutionarily adaptable.
期刊介绍:
The Journal of Chemical Health and Safety focuses on news, information, and ideas relating to issues and advances in chemical health and safety. The Journal of Chemical Health and Safety covers up-to-the minute, in-depth views of safety issues ranging from OSHA and EPA regulations to the safe handling of hazardous waste, from the latest innovations in effective chemical hygiene practices to the courts'' most recent rulings on safety-related lawsuits. The Journal of Chemical Health and Safety presents real-world information that health, safety and environmental professionals and others responsible for the safety of their workplaces can put to use right away, identifying potential and developing safety concerns before they do real harm.