当前位置:
X-MOL 学术
›
Chem. Commun.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Engineering terpene synthases and their substrates for the biocatalytic production of terpene natural products and analogues
Chemical Communications ( IF 4.3 ) Pub Date : 2024-12-28 , DOI: 10.1039/d4cc05785f Luke Alan Johnson, Rudolf K Allemann
Chemical Communications ( IF 4.3 ) Pub Date : 2024-12-28 , DOI: 10.1039/d4cc05785f Luke Alan Johnson, Rudolf K Allemann
Terpene synthases produce a wide number of hydrocarbon skeletons by controlling intramolecular rearragements of allylic pyrophosphate subtrates via reactive carbocation intermediates. Here we review recent research focused on engineering terpene synthases and modifying their substrates to rationally manipulate terpene catalyisis. Molecular dynamic simulations and solid state X-ray crystallography are powerful techniques to identify substrate binding modes, key active site residues for substrate folding, and the location of active site water. Variants in specific ‘hotspots’ of terpene synthases including the G1/2, K/H and H-1 helices have been targeted to modify active site water management and yield new products. We discuss the potential of exploiting substrate analogues to synthesise novel compounds and briefly outline biphasic flow systems for biocatalysis of terpenes. We forsee greater applications for terpenes as the field converges on effective methods for engingeering of terpene synthases by new computational and high throughput experimental methods and for high-yield production. It is crucial when engineering terpene synthases that both product distribution and enzyme activity are simultaneously optimised.
中文翻译:
用于生物催化生产萜烯天然产物和类似物的工程萜烯合酶及其底物
萜烯合酶通过反应性碳阳离子中间体控制烯丙基焦磷酸盐亚酸盐的分子内重新排列,从而产生大量的烃骨架。在这里,我们回顾了最近的研究,重点是工程萜烯合酶和修饰其底物以合理操纵萜烯 catalyisis。分子动力学模拟和固态 X 射线晶体学是识别底物结合模式、底物折叠的关键活性位点残基以及活性位点水位置的强大技术。萜烯合酶的特定“热点”中的变体,包括 G1/2、K/H 和 H-1 螺旋,已被靶向以改变活性位点水分管理并产生新产品。我们讨论了利用底物类似物合成新型化合物的潜力,并简要概述了用于萜烯生物催化的双相流系统。随着该领域趋于通过新的计算和高通量实验方法实现萜烯合酶的有效方法以及高产量生产,我们预计萜烯将有更大的应用。在设计萜烯合酶时,同时优化产品分布和酶活性至关重要。
更新日期:2024-12-28
中文翻译:
用于生物催化生产萜烯天然产物和类似物的工程萜烯合酶及其底物
萜烯合酶通过反应性碳阳离子中间体控制烯丙基焦磷酸盐亚酸盐的分子内重新排列,从而产生大量的烃骨架。在这里,我们回顾了最近的研究,重点是工程萜烯合酶和修饰其底物以合理操纵萜烯 catalyisis。分子动力学模拟和固态 X 射线晶体学是识别底物结合模式、底物折叠的关键活性位点残基以及活性位点水位置的强大技术。萜烯合酶的特定“热点”中的变体,包括 G1/2、K/H 和 H-1 螺旋,已被靶向以改变活性位点水分管理并产生新产品。我们讨论了利用底物类似物合成新型化合物的潜力,并简要概述了用于萜烯生物催化的双相流系统。随着该领域趋于通过新的计算和高通量实验方法实现萜烯合酶的有效方法以及高产量生产,我们预计萜烯将有更大的应用。在设计萜烯合酶时,同时优化产品分布和酶活性至关重要。