Department of Plant Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
Curr Opin Biotechnol. 2013 Apr;24(2):310-9. doi: 10.1016/j.copbio.2012.10.006. Epub 2012 Oct 26.
Recent advances in enzyme engineering enable dramatic improvements in catalytic efficiency and/or selectivity, as well as de novo engineering of enzymes to catalyze reactions where natural enzymes are not available. Can these capabilities be utilized to transform biosynthesis pathways? Metabolic engineering is traditionally based on combining existing enzymes to give new, or modified, pathways, within a new context and/or organism. How efficient, however, are the individual enzyme components? Is there room to improve pathway performance by enzyme engineering? We discuss the differences between enzymes in central versus specialized, or secondary metabolism and highlight unique features of specialized metabolism enzymes participating in the synthesis of natural products. We argue that, for the purpose of metabolic engineering, the catalytic efficiency and selectivity of many enzymes can be improved with the aim of achieving higher rates, yields and product purities. We also note the relative abundance of spontaneous reactions in specialized metabolism, and the potential advantage of engineering enzymes that will catalyze these steps. Specialized metabolism therefore offers new opportunities to integrate enzyme and pathway engineering, thereby achieving higher metabolic efficiencies, enhanced production rates and improved product purities.
近年来，酶工程的发展使得催化效率和/或选择性得到了显著提高，并且可以重新设计酶来催化天然酶无法催化的反应。这些能力能否用于改造生物合成途径？代谢工程传统上基于将现有的酶组合在一起，在新的背景和/或生物体中产生新的或修饰的途径。然而，单个酶成分的效率如何？通过酶工程是否有可能提高途径性能？我们讨论了中心代谢与专门代谢或次级代谢中酶的差异，并强调了参与天然产物合成的专门代谢酶的独特特征。我们认为，出于代谢工程的目的，可以提高许多酶的催化效率和选择性，以实现更高的速率、产率和产物纯度。我们还注意到专门代谢中自发反应的相对丰度，以及工程化能够催化这些步骤的酶的潜在优势。因此，专门代谢为整合酶和途径工程提供了新的机会，从而实现更高的代谢效率、提高生产速率和改善产物纯度。
