Cyanobacterial biofuels: new insights and strain design strategies revealed by computational modeling

Microbial Cell Factories

Research

Henning Knoop¹  Ralf Steuer¹  Philipp Erdrich²  Steffen Klamt² 

[1] Humboldt-University of Berlin, Institute for Theoretical Biology, Invalidenstraße 43, 10115, Berlin, Germany;Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstraße 1, 39106, Magdeburg, Germany;

关键词: Biofuels;    Metabolic engineering;    Cyanobacteria;    Minimal cut sets;    Photosynthesis;    Synechocystis sp. PCC 6803;   

DOI  :  10.1186/s12934-014-0128-x

 received in 2014-07-09, accepted in 2014-08-10,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundCyanobacteria are increasingly recognized as promising cell factories for the production of renewable biofuels and chemical feedstocks from sunlight, CO2, and water. However, most biotechnological applications of these organisms are still characterized by low yields. Increasing the production performance of cyanobacteria remains therefore a crucial step.ResultsIn this work we use a stoichiometric network model of Synechocystis sp. PCC 6803 in combination with CASOP and minimal cut set analysis to systematically identify and characterize suitable strain design strategies for biofuel synthesis, specifically for ethanol and isobutanol. As a key result, improving upon other works, we demonstrate that higher-order knockout strategies exist in the model that lead to coupling of growth with high-yield biofuel synthesis under phototrophic conditions. Enumerating all potential knockout strategies (cut sets) reveals a unifying principle behind the identified strain designs, namely to reduce the ratio of ATP to NADPH produced by the photosynthetic electron transport chain. Accordingly, suitable knockout strategies seek to block cyclic and other alternate electron flows, such that ATP and NADPH are exclusively synthesized via the linear electron flow whose ATP/NADPH ratio is below that required for biomass synthesis. The products of interest are then utilized by the cell as sinks for reduction equivalents in excess. Importantly, the calculated intervention strategies do not rely on the assumption of optimal growth and they ensure that maintenance metabolism in the absence of light remains feasible. Our analyses furthermore suggest that a moderately increased ATP turnover, realized, for example, by ATP futile cycles or other ATP wasting mechanisms, represents a promising target to achieve increased biofuel yields.ConclusionOur study reveals key principles of rational metabolic engineering strategies in cyanobacteria towards biofuel production. The results clearly show that achieving obligatory coupling of growth and product synthesis in photosynthetic bacteria requires fundamentally different intervention strategies compared to heterotrophic organisms.

【 授权许可】

Unknown   
© Erdrich et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.