Terpene cyclases are responsible for the initial cyclization cascade in the multistep synthesis of a large number of terpenes. CotB2 is a diterpene cyclase from Streptomyces melanosporofaciens, which catalyzes the formation of cycloocta-9-en-7-ol, a precursor to the next-generation anti-inflammatory drug cyclooctatin. In this work, we present evidence for the significant role of the active site's residues in CotB2 on the reaction energetics using quantum mechanical calculations in an active site cluster model. The results revealed the significant effect of the active site residues on the relative electronic energy of the intermediates and transition state structures with respect to gas phase data. A detailed understanding of the role of the enzyme environment on the CotB2 reaction cascade can provide important information towards a biosynthetic strategy for cyclooctatin and the biomanufacturing of related terpene structures.

中文翻译：

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使用聚类模型了解活性位点残基在CotB2催化中的作用。

萜烯环化酶负责大量萜烯的多步合成中的初始环化级联。CotB2是黑色链霉菌链霉菌中的一种二萜环化酶，可催化下一代抗炎药环辛汀的前体环辛9-9-en-7-ol的形成。在这项工作中，我们提供了证据，证明了在活性位点簇模型中使用量子力学计算，CotB2中活性位点残基对反应能学的显著作用。结果表明，相对于气相数据，活性位点残留物对中间体和过渡态结构的相对电子能量具有显着影响。