Graduate Program of Chemical Engineering, Federal University of São Carlos (PPGEQ-UFSCar), Rodovia Washington Luís, Km 235, São Carlos, SP, 13565-905, Brazil.
Graduate Program of Chemical Engineering-Institute of Chemistry, Federal University of Goiás (PPGEQ/IQ-UFG), Avenida Esperança, Campus Samambaia, Goiânia, GO, 74690-900, Brazil.
Microb Cell Fact. 2019 Sep 4;18(1):150. doi: 10.1186/s12934-019-1198-6.
Fine-tuning the aeration for cultivations when oxygen-limited conditions are demanded (such as the production of vaccines, isobutanol, 2-3 butanediol, acetone, and bioethanol) is still a challenge in the area of bioreactor automation and advanced control. In this work, an innovative control strategy based on metabolic fluxes was implemented and evaluated in a case study: micro-aerated ethanol fermentation.
The experiments were carried out in fed-batch mode, using commercial Saccharomyces cerevisiae, defined medium, and glucose as carbon source. Simulations of a genome-scale metabolic model for Saccharomyces cerevisiae were used to identify the range of oxygen and substrate fluxes that would maximize ethanol fluxes. Oxygen supply and feed flow rate were manipulated to control oxygen and substrate fluxes, as well as the respiratory quotient (RQ). The performance of the controlled cultivation was compared to two other fermentation strategies: a conventional "Brazilian fuel-ethanol plant" fermentation and a strictly anaerobic fermentation (with ultra-pure nitrogen used as the inlet gas). The cultivation carried out under the proposed control strategy showed the best average volumetric ethanol productivity (7.0 g L h), with a final ethanol concentration of 87 g L and yield of 0.46 g g . The other fermentation strategies showed lower yields (close to 0.40 g g ) and ethanol productivity around 4.0 g L h.
The control system based on fluxes was successfully implemented. The proposed approach could also be adapted to control several bioprocesses that require restrict aeration.
在需要氧气限制条件的培养物中（如疫苗、异丁醇、2-3 丁二醇、丙酮和生物乙醇的生产），对通气进行微调仍然是生物反应器自动化和高级控制领域的一个挑战。在这项工作中，实施了一种基于代谢通量的创新控制策略，并在一个案例研究中进行了评估：微曝气乙醇发酵。
实验在分批补料模式下进行，使用商业酿酒酵母、定义培养基和葡萄糖作为碳源。使用酿酒酵母基因组规模代谢模型的模拟来确定最大程度提高乙醇通量的氧气和基质通量范围。通过控制氧气供应和进料流量来控制氧气和基质通量以及呼吸商 (RQ)。将受控培养的性能与两种其他发酵策略进行了比较：传统的“巴西燃料乙醇厂”发酵和严格的厌氧发酵（使用超纯氮气作为入口气体）。根据所提出的控制策略进行的培养显示出最佳的平均体积乙醇生产率（7.0 g L h），最终乙醇浓度为 87 g L 和产率为 0.46 gg。其他发酵策略显示出较低的产率（接近 0.40 gg）和 4.0 g L h 左右的乙醇生产率。
成功实施了基于通量的控制系统。该方法还可以适应需要限制通气的几种生物过程的控制。
