Nybo S Eric, Khan Nymul E, Woolston Benjamin M, Curtis Wayne R
Department of Pharmaceutical Sciences, College of Pharmacy, Ferris State University, Big Rapids, MI, United States.
Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, United States.
Metab Eng. 2015 Jul;30:105-120. doi: 10.1016/j.ymben.2015.04.008. Epub 2015 May 8.
The ability of autotrophic organisms to fix CO2 presents an opportunity to utilize this 'greenhouse gas' as an inexpensive substrate for biochemical production. Unlike conventional heterotrophic microorganisms that consume carbohydrates and amino acids, prokaryotic chemolithoautotrophs have evolved the capacity to utilize reduced chemical compounds to fix CO2 and drive metabolic processes. The use of chemolithoautotrophic hosts as production platforms has been renewed by the prospect of metabolically engineered commodity chemicals and fuels. Efforts such as the ARPA-E electrofuels program highlight both the potential and obstacles that chemolithoautotrophic biosynthetic platforms provide. This review surveys the numerous advances that have been made in chemolithoautotrophic metabolic engineering with a focus on hydrogen oxidizing bacteria such as the model chemolithoautotrophic organism (Ralstonia), the purple photosynthetic bacteria (Rhodobacter), and anaerobic acetogens. Two alternative strategies of microbial chassis development are considered: (1) introducing or enhancing autotrophic capabilities (carbon fixation, hydrogen utilization) in model heterotrophic organisms, or (2) improving tools for pathway engineering (transformation methods, promoters, vectors etc.) in native autotrophic organisms. Unique characteristics of autotrophic growth as they relate to bioreactor design and process development are also discussed in the context of challenges and opportunities for genetic manipulation of organisms as production platforms.
自养生物固定二氧化碳的能力为利用这种“温室气体”作为生化生产的廉价底物提供了契机。与消耗碳水化合物和氨基酸的传统异养微生物不同，原核化能自养生物已进化出利用还原态化合物固定二氧化碳并驱动代谢过程的能力。代谢工程改造的商品化学品和燃料的前景，使得将化能自养宿主用作生产平台的应用得以复兴。诸如美国能源部高级研究计划局能源（ARPA - E）的电燃料项目等努力，凸显了化能自养生物合成平台所具有的潜力和障碍。本综述考察了化能自养代谢工程取得的诸多进展，重点关注氢氧化细菌，如典型的化能自养生物（罗尔斯通氏菌属）、紫色光合细菌（红杆菌属）和厌氧产乙酸菌。文中考虑了两种微生物底盘开发的替代策略：（1）在典型异养生物中引入或增强自养能力（碳固定、氢利用），或（2）改进天然自养生物中途径工程的工具（转化方法、启动子、载体等）。在将生物作为生产平台进行基因操作的挑战和机遇背景下，还讨论了自养生长与生物反应器设计和工艺开发相关的独特特性。
