Gallardo Roberto, Acevedo Alejandro, Quintero Julián, Paredes Ivan, Conejeros Raúl, Aroca Germán
Escuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaíso, Av. Brasil, 2085, Valparaíso, Chile.
Bioprocess Biosyst Eng. 2016 Feb;39(2):295-305. doi: 10.1007/s00449-015-1513-5. Epub 2015 Dec 9.
The biological production of butanol has become an important research field and thanks to genome sequencing and annotation; genome-scale metabolic reconstructions have been developed for several Clostridium species. This work makes use of the iCAC490 model of Clostridium acetobutylicum ATCC 824 to analyze its metabolic capabilities and response to an external electron supply through a constraint-based approach using the Constraint-Based Reconstruction Analysis Toolbox. Several analyses were conducted, which included sensitivity, production envelope, and phenotypic phase planes. The model showed that the use of an external electron supply, which acts as co-reducing agent along with glucose-derived reducing power (electrofermentation), results in an increase in the butanol-specific productivity. However, a proportional increase in the butyrate uptake flux is required. Besides, the uptake of external butyrate leads to the coupling of butanol production and growth, which coincides with results reported in literature. Phenotypic phase planes showed that the reducing capacity becomes more limiting for growth at high butyrate uptake fluxes. An electron uptake flux allows the metabolism to reach the growth optimality line. Although the maximum butanol flux does not coincide with the growth optimality line, a butyrate uptake combined with an electron uptake flux would result in an increased butanol volumetric productivity, being a potential strategy to optimize the production of butanol by C. acetobutylicum ATCC 824.
丁醇的生物生产已成为一个重要的研究领域,得益于基因组测序和注释,已为多种梭菌属物种开发了基因组规模的代谢重建模型。这项工作利用丙酮丁醇梭菌ATCC 824的iCAC490模型,通过使用基于约束的重建分析工具箱的基于约束的方法,分析其代谢能力和对外部电子供应的响应。进行了多项分析,包括敏感性分析、生产包络分析和表型相平面分析。该模型表明,使用外部电子供应作为共还原剂与葡萄糖衍生的还原力一起作用(电发酵),会导致丁醇比生产率提高。然而,丁酸摄取通量需要成比例增加。此外,摄取外部丁酸会导致丁醇生产与生长的耦合,这与文献报道的结果一致。表型相平面表明,在高丁酸摄取通量下,还原能力对生长的限制更大。电子摄取通量使代谢能够达到生长最优线。虽然最大丁醇通量与生长最优线不一致,但丁酸摄取与电子摄取通量相结合将导致丁醇体积生产率提高,这是优化丙酮丁醇梭菌ATCC 824丁醇生产的一种潜在策略。