Hibbert Edward G, Baganz Frank, Hailes Helen C, Ward John M, Lye Gary J, Woodley John M, Dalby Paul A
Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK.
Biomol Eng. 2005 Jun;22(1-3):11-9. doi: 10.1016/j.bioeng.2004.09.003.
The benefits of applying biocatalysts to organic synthesis, such as their high chemo-, regio-, and enantio-specificity and selectivity, must be seriously considered, especially where chemical routes are unavailable, complex or prohibitively expensive. In cases where a potential biocatalytic route is not yet efficient enough to compete with chemical synthesis, directed evolution, and/or process engineering could be implemented for improvements. While directed evolution has demonstrated great potential to enhance enzyme properties, there will always be some aspects of biocatalytic processes that it does not address. Even where it can be successfully applied, the resources required for its implementation must currently be weighed against the feasibility of, and resources available for developing a chemical synthesis route. Here, we review the potential of combining directed evolution with process engineering, and recent developments to improve their implementation. Favourable targets for the directed evolution of new biocatalysts are the syntheses of highly complex molecules, especially where chemistry, metabolic engineering or recombineering provide a partial solution. We also review some of the recent advances in the application of these approaches alongside the directed evolution of biocatalysts.
必须认真考虑将生物催化剂应用于有机合成的好处，例如其高化学、区域和对映体特异性及选择性，特别是在化学路线不可行、复杂或成本过高的情况下。在潜在的生物催化路线效率尚不足以与化学合成竞争的情况下，可以实施定向进化和/或过程工程来加以改进。虽然定向进化已显示出增强酶特性的巨大潜力，但生物催化过程的某些方面它仍无法解决。即使在能够成功应用的情况下，目前也必须权衡实施定向进化所需的资源与开发化学合成路线的可行性及可用资源。在此，我们综述将定向进化与过程工程相结合的潜力以及近期为改进其实施所取得的进展。新生物催化剂定向进化的有利目标是合成高度复杂的分子，尤其是在化学、代谢工程或重组工程只能提供部分解决方案的情况下。我们还综述了这些方法与生物催化剂定向进化一起应用的一些最新进展。
