An ancient Chinese wisdom for metabolicengineering: Yin-Yang

Microbial Cell Factories

Review

Yinjie J Tang¹  Stephen G Wu¹  Lian He¹  Qingzhao Wang² 

[1] Department of Energy, Environmental and Chemical Engineering, Washington University, 63130, St. Louis, MO, USA;Fine Chemicals & Biocatalysis Research, BASF Corporation, 10591, Tarrytown, NY, USA;

关键词: ATP;    Energy metabolism;    Flux analysis;    Free energy;    Maintenance loss;    Semi-biosynthesis;   

DOI  :  10.1186/s12934-015-0219-3

 received in 2014-11-03, accepted in 2015-03-02,  发布年份 2015

来源: Springer

【 摘 要 】

In ancient Chinese philosophy, Yin-Yang describes two contrary forcesthat are interconnected and interdependent. This concept also holds true inmicrobial cell factories, where Yin represents energy metabolism in the form of ATP,and Yang represents carbon metabolism. Current biotechnology can effectively editthe microbial genome or introduce novel enzymes to redirect carbon fluxes. On theother hand, microbial metabolism loses significant free energy as heat whenconverting sugar into ATP; while maintenance energy expenditures further aggravateATP shortage. The limitation of cell “powerhouse” prevents hosts from achieving highcarbon yields and rates. Via an Escherichia coliflux balance analysis model, we further demonstrate the penalty of ATP cost onbiofuel synthesis. To ensure cell powerhouse being sufficient in microbial cellfactories, we propose five principles: 1. Take advantage of native pathways forproduct synthesis. 2. Pursue biosynthesis relying only on pathways or genetic partswithout significant ATP burden. 3. Combine microbial production with chemicalconversions (semi-biosynthesis) to reduce biosynthesis steps. 4. Create “minimalcells” or use non-model microbial hosts with higher energy fitness. 5. Develop aphotosynthesis chassis that can utilize light energy and cheap carbon feedstocks.Meanwhile, metabolic flux analysis can be used to quantify both carbon and energymetabolisms. The fluxomics results are essential to evaluate the industrialpotential of laboratory strains, avoiding false starts and dead ends duringmetabolic engineering.

【 授权许可】

Unknown   
© Wu et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of theCreative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproductionin any medium, provided the original work is properly credited. The CreativeCommons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unlessotherwise stated.