生物信息学在工业生物催化研究中的应用

随着石油等不可再生资源的日益减少以及环境污染问题的日益严重,应用工业生物催化技术改造或取代传统化工工艺已经成为新世纪化学工业可持续发展的研究热点。工业生物催化技术的研究对象是生物催化剂及其催化过程。近来,利用生物信息学技术进行工业生物催化研究已经越来越受到人们的重视。随着工业生物催化的发展,生物信息学将直接指导并加快新型高效生物催化剂的发现及功能改造进程。     

生物催化技术研究现状和发展趋势

正生物催化技术是当今国际科技发展的热点,将继信息技术后引领新一轮的全球科技革命。文章介绍了近年来国内外生物催化技术的最新研究进展和发展趋势,包括生物催化剂的发现与改造、生物催化机理、生物合成反应的设计与调控、生物催化系统的设计和构建,以及生物催化技术的工业应用实例等。     

有机化合物生物催化研究进展

随着近十几年来工业生物技术的发展,有机化合物的生物催化也取得了飞速的进步.近几年的研究集中在:新生物催化剂的筛选和酶的定向改造;非水相生物催化中酶有机溶剂耐受性的增强和非传统介质的应用;生物催化在手性化合物,药物等精细化学品领域的应用;组合生物催化作为组合化学和生物催化相结合而成的一个新技术生长点,并取得一定的进展,为新药的开发提供一种切实可行的方法.     

生物催化剂的发现及改造

生物催化剂是限制工业生物催化的重要瓶颈,发现新型生物催化剂或生物催化剂的新功能及新底物是目前的主要任务。实现该目标的方法有三种:(1)从环境样品中筛选,(2)利用蛋白质工程改造现有生物催化剂,(3)探寻现有生物催化剂的新功能。本文描述了上述三种方法的关键步骤及技术,其中重点介绍了高通量培养技术以及新近发展起来的半理性设计改造生物催化剂的技术。     

工业生物催化技术在绿色精细化学品合成中的机遇

生物催化技术具有反应条件温和、专一性强、环境友好等特点,是传统化学方法无法比拟的。本文从生物催化技术的特点及其在精细化学品合成中的应用现状出发,从产品战略、技术策略等方面提出生物催化技术应用的方向与目标：生物催化与有机合成技术的集成、交叉将会是未来生物催化技术发展的重要方向;有机合成技术为生物催化技术的发展、应用指明并提供了更多技术、产品及产业机会。     

精细化学品绿色合成用工具酶酌定向开发

近年来随着人们环境保护意识的增强以及对可持续发展技术的追求,使得以绿色环保为特色的生物催化技术越来越受到人们的关注。生物催化剂作为生物催化技术的工具,发挥着至关重要的核心作用。本文综述了生物催化技术发展各个阶段生物催化剂定向开发的最新进展。     

酶及其生物催化技术的研究与应用

与传统化学催化工艺相比,基于酶的生物催化工艺具有反应条件温和、环境友好、操作简便、立体选择性优良等优势。当前已有多个生物催化工艺应用于生产精细大宗化学品和高附加值医药中间体,此外在食品、化妆品等领域也有广泛的应用。主要综述了酶及其生物催化技术的研究进展,包括酶序的构建、酶的定向进化,以及酶与生物催化技术在大宗化学品、医药中间体、食品、化妆品、纺织以及纸浆造纸工业中的应用。     

手性医药化学品生物催化绿色制造

生物催化具有选择性强、催化效率高、反应条件温和、环境友好等优点,广泛应用于传统化学方法不能或者不易合成的手性化合物的生产过程中,已成为化学合成法的一种重要补充。同时,生物催化能够更好地解决资源、能源和环境方面的压力,维持和谐的生态环境,促进工业的可持续发展。近年来,生物催化技术已在手性医药化学品产业化生产中得到了广泛的应用,有效地实现了手性医药化学品的绿色制造。本文就生物催化介入的手性医药化学品的产业化技术和过程进行介绍。     

Ribozyme与基因表达

Ribozyme指一类具有生物催化功能的RNA,也称RNA催化剂、在化学本质上,它不同于具有生物催化功能的蛋白质--酶(enzyme),Ribozyme发现于80年代初,近十年来,ribozyme研究进展深化了生物催化理论,提出了生物大分子和生命起源的新概念。     

改进酶稳定性的定向进化技术

酶作为一种生物催化剂,以其独特的优良特性,在绿色化学和清洁生产中得到了广泛的应用。随着酶定向进化技术的建立和发展,通过定向进化改进酶稳定性的研究越来越多。详细综述了各种定向进化方法的特点及在提高酶稳定性方面的应用,并从结构和功能的角度进一步解释了相关机理。     

Biocatalysis for the synthesis of pharmaceuticals and pharmaceutical intermediates

Biocatalysis has been increasingly used for pharmaceutical synthesis in an effort to make manufacturing processes greener and more sustainable. Biocatalysts that possess excellent activity, specificity, thermostability and solvent-tolerance are highly sought after to meet the requirements of practical applications. Generating biocatalysts with these specific properties can be achieved by either discovery of novel biocatalysts or protein engineering. Meanwhile, chemoenzymatic routes have also been designed and developed for pharmaceutical synthesis on an industrial scale. This review discusses the recent discoveries, engineering, and applications of biocatalysts for the synthesis of pharmaceuticals and pharmaceutical intermediates. Key classes of biocatalysts include reductases, oxidases, hydrolases, lyases, isomerases, and transaminases.     

A window into biocatalysis and biotransformations

Eight papers were presented in this year's symposium "Advances in Biocatalysis" at the 232nd ACS National Meeting, accentuating the most recent development in biocatalysis. Researchers from both industry and academia are addressing several fundamental problems in biocatalysis, including the limited number of commercially available enzymes that can be provided in bulk quantities, the limited enzyme stability and activity in nonaqueous environments, and the permeability issue and cell localization problems in whole-cell systems. A trend that can be discerned from these eight talks is the infusion of new tools and technologies in addressing various challenges facing biocatalysis. Nanotechnology, bioinformatics, cellular membrane engineering and metabolic engineering (for engineering whole-cell catalysts), and protein engineering (to improve enzymes and create novel enzymes) are becoming more routinely used in research laboratories and are providing satisfactory solutions to the problems in biocatalysis. Significant progress in various aspects of biocatalysis from discovery to industrial applications was highlighted in this symposium.     

Recent advances in biocatalyst discovery,development and applications

Enzymes catalyze a wide range of biotransformations and have a great potential as environmentally friendly alternatives to classical chemical catalysts in various industrial applications. Recently, advanced techniques and strategies in enzyme discovery and engineering have led to the significant expansion of the quantity and functional diversity of biocatalysts, which has further allowed broader uses of biocatalysts in new processes, especially those traditionally enabled only by chemical catalysts. Here we highlight some of these recent advances with the focus on new approaches in biocatalyst discovery and development, and discuss new applications of selected biocatalysts including transaminases, cytochrome P450s, and Baeyer–Villiger monooxygenases.     

Are Lipases Still Important Biocatalysts? A Study of Scientific Publications and Patents for Technological Forecasting

The great potential of lipases is known since 1930 when the work of J. B. S. Haldane was published. After eighty-five years of studies and developments, are lipases still important biocatalysts? For answering this question the present work investigated the technological development of four important industrial sectors where lipases are applied: production of detergent formulations; organic synthesis, focusing on kinetic resolution, production of biodiesel, and production of food and feed products. The analysis was made based on research publications and patent applications, working as scientific and technological indicators, respectively. Their evolution, interaction, the major players of each sector and the main subject matters disclosed in patent documents were discussed. Applying the concept of technology life cycle, S-curves were built by plotting cumulative patent data over time to monitor the attractiveness of each technology for investment. The results lead to a conclusion that the use of lipases as biocatalysts is still a relevant topic for the industrial sector, but developments are still needed for lipase biocatalysis to reach its full potential, which are expected to be achieved within the third, and present, wave of biocatalysis.     

非水酶学和非水相生物催化研究进展

近年来工业生物技术飞速发展,酶学和生物催化领域也取得突破性进展,特别在酶在非水相中活性及稳定性研究,耐溶剂生物催化剂的筛选、构建、修饰和改造,生物相容性和环境相容性好的绿色介质等方面取得了较大的进展。最近的研究热点和未来几年的研究方向主要为:基于基因组信息的耐溶剂酶的虚拟筛选和构建;基于自然界筛选新酶基因的耐溶剂酶重构和改造;离子液体等环境友好的绿色介质系统等几个方面。     

Biocatalysis in drug discovery and development

Enzyme catalysis, enabled by advances in protein engineering and directed evolution, is beginning to transform chemical synthesis in the pharmaceutical industry. This review presents recent examples of the creative use of biocatalysis to enable drug discovery and development. We illustrate how increased access to novel biotransformations and the rise of cascade biocatalysis allowed fundamentally new syntheses of novel medicines, representing progress toward more sustainable pharmaceutical manufacturing. Finally, we describe the opportunities and challenges the industry must address to ensure the reduction to practice of biotechnological innovations to develop new therapies in a faster, more economical, and environmentally benign way.     

生物催化与生物转化研究进展

由于生物催化过程具有高效、高选择性、条件温和、环境友好等优点,因此成为可持续发展过程中替代和拓展传统有机化学合成的重要方法。近两年的进展集中于新生物催化剂的发现和改造,以及将生物催化和生物转化应用于工业过程的探索,包括开发新的反应体系,新的固定化方法等。可以预见,在医药中间体等高附加值化工产品的生产过程中,生物催化和生物转化的应用将呈现加速增长趋势。     

Biocatalysts: Beautiful creatures

The chemical industry has come under increasing pressure to make chemical production more eco-friendly and independent to fossil resources. The development of industrial processes based on micro-organisms can especially help to eliminate the use or the generation of hazardous substances and can support the transition from dependence on fossil resources towards real sustainable and eco-safety industrial processes. The biocatalysts are the best solution given by nature that can be used to improve some biotechnological applications. In this research review, we report some peculiar properties of biocatalysts, implicated in a range of metabolic pathways and biotechnological tools.     

3-脱氢莽草酸生物合成的代谢工程

3-脱氢莽草酸,是芳香族氨基酸生物合成代谢途径中一种重要的中间产物,可作为一些化学合成制剂和药物中间原料。这样以无毒可再生物质为起始原料的合成方法与传统的有机合成化学制剂的方法相比,对环境更加有利。此外,它还是一种十分有效的抗氧化剂。工业上一般采用化学合成法和发酵法来生产3-脱氢莽草酸,随着代谢工程的兴起,使得更加理性改造菌株成为可能,这更加促进了发酵法的广泛应用。本文主要介绍了代谢工程在生物合成3-脱氢莽草酸生产菌改造中的应用情况,其中涉及3-脱氢莽草酸生物合成途径中相关基因及其酶的调控、中心代谢途径的改造和3-脱氢莽草酸合成支路的修饰等,并探讨了将来的发展前景。