The diauxic growth of Saccharomyces cerevisiae on glucose and xylose during cellulose-to-ethanol processes extends the duration of the fermentation and reduces productivity. Despite the remarkable advances in strain engineering, the co-consumption of glucose and xylose is still limited due to catabolite repression. This work addresses this challenge by developing a closed-loop controller that is capable of maintaining the glucose concentration at a steady set-point during fed-batch fermentation. The suggested controller uses a data-driven model to measure the concentration of glucose from ‘real-time’ spectroscopic data. The concentration of glucose is then automatically controlled using a control scheme that consists of a proportional, integral, differential (PID) algorithm and a supervisory layer that manipulates the feed-rates to the reactor accounting for the changing dynamics of fermentation. The PID parameters and the supervisory layer were progressively improved throughout four fed-batch lignocellulosic-to-ethanol fermentations to attain a robust controller able of maintaining the glucose concentration at the pre-defined set-points. The results showed an increased co-consumption of glucose and xylose that resulted in volumetric productivities that are 20–33% higher than the reference batch processes. It was also observed that fermentations operated at a glucose concentration of 10 g/L were faster than those operated at 4 g/L, indicating that there is an optimal glucose concentration that maximises the overall productivity. Promoting the simultaneous consumption of glucose and xylose in S. cerevisiae is critical to increase the productivity of lignocellulosic ethanol processes, but also challenging due to the strong catabolite repression of glucose on the uptake of xylose. Operating the fermentation at low concentrations of glucose allows reducing the effects of the catabolite repression to promote the co-consumption of the two carbon sources. However, S. cerevisiae is very sensitive to changes in the glucose concentration and deviations from a set-point result in notable productivity losses. The controller structure developed and implemented in this work illustrates how combining data-driven measurements of the glucose concentration and a robust yet effective PID-based supervisory control allowed tight control of the concentration of glucose to adjust it to the metabolic requirements of the cell culture that can unlock tangible gains in productivities.

中文翻译：

---

使用数据驱动的反馈控制器促进木质纤维素纤维素发酵中葡萄糖和木糖的联合利用

在纤维素转化为乙醇的过程​​中，酿酒酵母在葡萄糖和木糖上的双生生长延长了发酵时间并降低了生产率。尽管菌株工程技术取得了显着进步，但是由于分解代谢物的抑制，葡萄糖和木糖的共同消耗仍然受到限制。这项工作通过开发一种闭环控制器来解决这一挑战，该控制器能够在分批补料发酵过程中将葡萄糖浓度维持在稳定的设定点。建议的控制器使用数据驱动模型从“实时”光谱数据中测量葡萄糖浓度。然后，使用一种由比例，积分，差分（PID）算法和控制层，该层可控制反应器的进料速度，从而解决发酵过程中不断变化的动态问题。在四个分批补料的木质纤维素至乙醇发酵过程中，PID参数和监控层都得到了逐步改善，从而获得了一个鲁棒的控制器，能够将葡萄糖浓度维持在预定的设定点。结果表明，葡萄糖和木糖的共同消耗量增加，导致容积生产率比参考批生产过程高20-33％。还观察到，在10 g / L的葡萄糖浓度下进行的发酵比在4 g / L的葡萄糖下进行的发酵要快，这表明存在最佳的葡萄糖浓度，可以使总生产率最大化。促进酿酒酵母中葡萄糖和木糖的同时消耗对于提高木质纤维素乙醇工艺的生产率至关重要，但由于对木糖的吸收强烈地分解代谢抑制葡萄糖，因此也具有挑战性。在低浓度的葡萄糖下进行发酵可以降低分解代谢物抑制的作用，从而促进两种碳源的共同消耗。但是，酿酒酵母对葡萄糖浓度的变化非常敏感，偏离设定点会导致生产力显着下降。