The biomanufacturing industry has now the opportunity to upgrade its production processes to be in harmony with the latest industrial revolution. Technology creates capabilities that enable smart manufacturing while still complying with unfolding regulations. However, many biomanufacturing companies, especially in the biopharma sector, still have a long way to go to fully benefit from smart manufacturing as they first need to transition their current operations to an information-driven future. One of the most significant obstacles towards the implementation of smart biomanufacturing is the collection of large sets of relevant data. Therefore, in this work, we both summarize the advances that have been made to date with regards to the monitoring and control of bioprocesses, and highlight some of the key technologies that have the potential to contribute to gathering big data. Empowering the current biomanufacturing industry to transition to Industry 4.0 operations allows for improved productivity through information-driven automation, not only by developing infrastructure, but also by introducing more advanced monitoring and control strategies.

The high substrate variability and complexity of fermentation media derived from lignocellulosic feedstock affects the concentration profiles and the length of the fermentation. Failing to account for such variability raises operational and scheduling issues and affects the overall performance of these processes. In this work, a hybrid soft sensor was developed to monitor and forecast the evolution of cellulose‐to‐ethanol fermentation. The soft sensor consisted of two modules (a data‐driven model and a kinetic model) connected sequentially. The data‐driven module used a partial‐least‐squares model to estimate the current state of glucose from spectroscopic data. The kinetic model was recursively fitted to known concentrations of glucose to update the long‐horizon predictions of glucose, xylose, and ethanol. This combination of real‐time data update from an actual fermentation process to a high‐fidelity kinetic model constitutes the basis of the digital twin concept and allows for a better real‐time understanding of complex inhibition phenomena caused by different inhibitors commonly found in lignocellulosic feedstocks. The soft sensor was experimentally validated with three different cellulose‐to‐ethanol fermentations and the results suggested that this method is suitable for monitoring and forecasting fermentation when the measurements provide reasonably good estimates of the real state of the system. These results would allow the flexibility of the operation of cellulosic processes to be increased, and would permit the scheduling to be adapted to the inherent variability of such substrates © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.

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Many anaerobic conversions proceed close to thermodynamic equilibrium and the microbial groups involved need to share their low energy budget to survive at the thermodynamic boundary of life. This study aimed to investigate the kinetic and thermodynamic control mechanisms of the electron transfer during syntrophic butyrate conversion in non-defined methanogenic communities. Despite the rather low energy content of butyrate, results demonstrate unequal energy sharing between the butyrate-utilizing species (17 %), the hydrogenotrophic methanogens (9–10 %), and the acetoclastic methanogens (73–74 %). As a key finding, the energy disproportion resulted in different growth strategies of the syntrophic partners. Compared to the butyrate-utilizing partner, the hydrogenotrophic methanogens compensated their lower biomass yield per mole of electrons transferred with a 2-fold higher biomass-specific electron transfer rate. Apart from these thermodynamic control mechanisms, experiments revealed a ten times lower hydrogen inhibition constant on butyrate conversion than proposed by the Anaerobic Digestion Model No. 1, suggesting a much stronger inhibitory effect of hydrogen on anaerobic butyrate conversion. At hydrogen partial pressures exceeding 40 Pa and at bicarbonate limited conditions, a shift from methanogenesis to reduced product formation was observed which indicates an important role of the hydrogen partial pressure in redirecting electron fluxes towards reduced products such as butanol. The findings of this study demonstrate that a careful consideration of thermodynamics and kinetics is required to advance our current understanding of flux regulation in energy-limited syntrophic ecosystems.Electronic supplementary materialThe online version of this article (doi:10.1007/s00253-015-6971-9) contains supplementary material, which is available to authorized users.

In this study, the impact of the hydrogen partial pressure on lactate degradation was investigated in a coculture of Desulfovibrio sp. G11 and Methanobrevibacter arboriphilus DH1. To impose a change of the hydrogen partial pressure, formate was added to the reactor. Hydrogen results from the bioconversion of formate besides lactate in the liquid phase. In the presence of a hydrogen-consuming methanogen, this approach allows for a better estimation of low dissolved hydrogen concentrations than under conditions where hydrogen is supplied externally from the gas phase, resulting in a more accurate determination of kinetic parameters. A change of the hydrogen partial pressure from 1,200 to 250 ppm resulted in a threefold increase of the biomass-specific lactate consumption rate. The 50 % inhibition constant of hydrogen on lactate degradation was determined as 0.692 ± 0.064 μM dissolved hydrogen (831 ± 77 ppm hydrogen in the gas phase). Moreover, for the first time, the maximum biomass-specific lactate consumption rate of Desulfovibrio sp. G11 (0.083 ± 0.006 mol-Lac/mol-XG11/h) and the affinity constant for hydrogen uptake of Methanobrevibacter arboriphilus DH1 (0.601 ± 0.022 μM dissolved hydrogen) were determined. Contrary to the widely established view that the biomass-specific growth rate of a methanogenic coculture is determined by the hydrogen-utilizing partner; here, it was found that the hydrogen-producing bacterium determined the biomass-specific growth rate of the coculture grown on lactate and formate.