Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Trends Biotechnol. 2020 Jul;38(7):811-822. doi: 10.1016/j.tibtech.2020.03.009. Epub 2020 Apr 29.
Metabolic engineering has emerged as an important tool for reconstructing heterologous isoprenoid metabolic pathways in microbial hosts. Here, we provide an overview of promising engineering strategies that have proven to be successful for the high-yield production of isoprenoids. Besides 'conventional' approaches, such as the 'push-pull' and protein engineering to optimize the isoprenoid flux and limited catalytic activity of enzymes, we review emerging strategies in the field, including compartmentalization between synthetic consortia members, novel bypass pathways for isoprenoid synthesis, cell-free systems, and improvement of the lipid content to overcome storage isoprenoid limitations. Pitfalls, along with lessons learned from the application of these strategies, will be addressed with the hope of guiding future efforts toward cost-effective and sustainable production of isoprenoids.
代谢工程已成为在微生物宿主中重建异源类异戊二烯代谢途径的重要工具。在这里，我们提供了一些有前途的工程策略的概述，这些策略已被证明可成功地用于高产异戊二烯。除了“常规”方法，如“推-拉”和蛋白质工程来优化类异戊二烯通量和酶的有限催化活性外，我们还回顾了该领域的新兴策略，包括合成联合体成员之间的区室化、用于异戊二烯合成的新旁路途径、无细胞系统以及提高脂质含量以克服储存异戊二烯的限制。我们将讨论这些策略的应用所带来的陷阱以及从中吸取的教训，希望能为未来以具有成本效益和可持续性的方式生产异戊二烯提供指导。
