Kempinski Chase, Jiang Zuodong, Bell Stephen, Chappell Joe
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, 40536, USA.
Adv Biochem Eng Biotechnol. 2015;148:161-99. doi: 10.1007/10_2014_290.
Isoprenoids are a class of compounds derived from the five carbon precursors, dimethylallyl diphosphate, and isopentenyl diphosphate. These molecules present incredible natural chemical diversity, which can be valuable for humans in many aspects such as cosmetics, agriculture, and medicine. However, many terpenoids are only produced in small quantities by their natural hosts and can be difficult to generate synthetically. Therefore, much interest and effort has been directed toward capturing the genetic blueprint for their biochemistry and engineering it into alternative hosts such as plants and algae. These autotrophic organisms are attractive when compared to traditional microbial platforms because of their ability to utilize atmospheric CO2 as a carbon substrate instead of supplied carbon sources like glucose. This chapter will summarize important techniques and strategies for engineering the accumulation of isoprenoid metabolites into higher plants and algae by choosing the correct host, avoiding endogenous regulatory mechanisms, and optimizing potential flux into the target compound. Future endeavors will build on these efforts by fine-tuning product accumulation levels via the vast amount of available "-omic" data and devising metabolic engineering schemes that integrate this into a whole-organism approach. With the development of high-throughput transformation protocols and synthetic biology molecular tools, we have only begun to harness the power and utility of plant and algae metabolic engineering.
类异戊二烯是一类由五碳前体物质——二甲基烯丙基二磷酸酯和异戊烯基二磷酸酯衍生而来的化合物。这些分子呈现出令人难以置信的天然化学多样性,在化妆品、农业和医学等诸多方面对人类具有重要价值。然而,许多萜类化合物仅由其天然宿主少量产生,且难以通过合成方式生成。因此,人们对获取其生物化学的遗传蓝图并将其导入植物和藻类等替代宿主投入了大量的关注和努力。与传统微生物平台相比,这些自养生物具有吸引力,因为它们能够利用大气中的二氧化碳作为碳底物,而不是像葡萄糖这样的外源供应碳源。本章将总结通过选择合适的宿主、规避内源性调控机制以及优化进入目标化合物的潜在通量,将类异戊二烯代谢产物积累工程导入高等植物和藻类的重要技术和策略。未来的努力将基于这些工作,通过利用大量可用的“组学”数据微调产物积累水平,并设计将其整合到全生物体方法中的代谢工程方案。随着高通量转化方案和合成生物学分子工具的发展,我们才刚刚开始利用植物和藻类代谢工程的力量和效用。