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Status of protein engineering for biocatalysts: How to design an industrially useful biocatalyst

机译:生物催化剂蛋白质工程的现状:如何设计工业上有用的生物催化剂

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摘要

Recent advances in the development of both experimental and computational protein engineering tools have enabled a number of further successes in the development of biocatalysts ready for large-scale applications. Key tools are first, the targeting of libraries, leading to far smaller but more useful libraries than in the past, second, the combination of structural, mechanistic, and sequence-based knowledge often based on prior successful cases, and third, the advent of structurally based algorithms allowing the design of novel functions. Based on these tools, a number of improved biocatalysts for pharmaceutical applications have been presented, such as an (R)-transaminase for the synthesis of active pharmaceutical ingredients (APIs) of sitagliptin (Januvia~?) and ketoreductases, glucose dehydrogenases, and haloalkane dehalogenases for the API synthesis toward atorvastatin (Lipitor~?) and montelukast (Singulair~?).
机译:实验性和计算性蛋白质工程工具的开发方面的最新进展,使得在准备用于大规模应用的生物催化剂的开发方面取得了许多进一步的成功。关键工具是:首先,针对库进行开发,从而导致比过去更小但更有用的库;其次,通常基于先前的成功案例,结合基于结构,机制和基于序列的知识,其次,第三,库的出现。基于结构的算法,允许设计新颖的功能。基于这些工具,已经提出了许多用于药物应用的改良生物催化剂,例如用于合成西他列汀(Januvia?)和酮还原酶,葡萄糖脱氢酶和卤代烷烃的活性药物成分(API)的(R)-转氨酶。用于阿托伐他汀(Lipitor?)和孟鲁司特(Singulair?)的API合成的脱卤酶。

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