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A.J.J. Straathof

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This study advances the development of syngas fermentation by presenting the first industrial-scale process design for producing isopropanol (IPA) and acetone from steel mill off-gas, with a total production capacity of 46–50 ktonne per year. The process was rigorously developed in Aspen Plus, with a comprehensive techno-economic assessment and life-cycle analysis performed to evaluate the process performance. The developed process maximizes energy efficiency by utilizing the heat content of steel off-gas and implementing advanced heat pump systems. As a result, the process is thermally self-sufficient and can operate solely on renewable electricity. Efficient utilization of waste gases results in substantial reductions in global warming potential compared with petrochemical-based production (144–160% for IPA and 138–149% for acetone). The unit production cost of 0.58–0.74 $/kgIPA/Ac and potential profit margins of 49–65% testify to the cost-effectiveness of the developed process. These findings demonstrate the environmental and economic sustainability of syngas fermentation from steel mill off-gas, establishing it as a potentially viable alternative to conventional petrochemical processes. This technology may hold great potential in reducing environmental impacts and carbon emissions in industrial chemical production. ...
Journal article (2025) - Mungyu Lee, Tamara Jankovic, Francisco Caparrós-Salvador, Ludovic Jourdin, Adrie J.J. Straathof
Carbon dioxide utilization is a key strategy for sustainable chemical production and climate change mitigation. Microbial electrosynthesis (MES) offers a promising approach to convert CO₂ into organic acids and multi‑carbon compounds, but its industrial application requires improved product recovery methods. In this study, we developed an integrated MES-sorption-distillation system for the recovery of pure hexanoic acid. Adsorption experiments identified conditions for C6-selective capture from C2–C6 carboxylate mixtures typically produced from MES. Subsequent desorption using CO₂ expanded methanol enriched hexanoic acid concentration by 13-fold compared to the aqueous feed, achieving 67 % recovery in a single pass, but 100 % overall, since recirculation of unrecovered carboxylates back to the MES reactor is proposed. This recirculation will enhance chain elongation, eliminate loss of unrecovered carboxylates, and reduce the need for external pH control during MES. Distillation of the desorbed mixture led to streams of pure products and reusable solvent, without losses. Notably, 87 % of the total energy demand for product formation is attributed to the MES stage, where electrical energy is directly supplied as electrons to drive microbial production. Thus, MES with the proposed recovery method enables pure hexanoic acid production with minimal losses of materials or energy and potentially allows the system to operate in a carbon-negative manner. ...

Towards a rapid modeling approach for fed-batch fermentations

Anticipating the occurrence and effects of mass transport limitations during fermentation scale-up is essential for commercialization, as heterogeneities might affect microorganisms. Tools like Computational Fluid Dynamics (CFD) aid this analysis but are computationally intensive, limiting design space exploration and consequently, fermentation optimization. Compartment models (CMs) based on CFD simulations offer an affordable alternative but require CFD recalibration with changing geometries or operating conditions, restricting their usage in optimization.
In this work, we introduce a hybrid machine-learning-aided compartment model (ML-CM) that accounts for flow pattern dynamics upon changes in both volume and stirring speed in a stirred tank bioreactor. The ML-aided dynamic compartment model (dyn-CM) enabled the spatiotemporal study of a process in 1/500th of the fermentation simulation time, maintaining reasonable accuracy. This method facilitates fed-batch fermentation modeling, process optimization, and scale-up effect analysis with modest computational resources, supporting reactor design and operational improvements within a defined operating space. ...
The butanediols (BDOs), 2,3-, 1,4- and 1,3-butanediol, are platform chemicals that are mainly produced from fossil hydrocarbons but may be obtained through fermentation. However, low product concentration, by-product formation and high boiling temperatures of BDOs hinder downstream processing and increase overall fermentation costs. This study increases the competitiveness of industrial biotechnology by designing a large-scale process (broth processing capacity of 160 ktonne/y) for the final purification of BDOs after fermentation (recovery >99 %). It includes an initial preconcentration step in a vacuum distillation column to remove most water and light impurities. The initial removal of most of the water and the use of a heat pump system allowed significant energy reduction. At the heart of the process is an integrated dividing-wall column that can efficiently purify BDO from the remaining light and heavy impurities. Moreover, a single process design was proven effective in purifying different BDOs to > 99.4 wt%. This was cost-effective (total purification costs of 0.208 – 0.243 $/kgBDO) and energy-efficient (with primary energy requirements of 1.854 – 2.176 kWthh/kgBDO). The proposed purification sequence can be used for each BDO type, which offers flexibility in developing sustainable bioprocesses for BDO production. ...
Journal article (2025) - Marijn J. Timmer, Maria Inês Vaz, Jolien De Paepe, Iris Jiaqi De Corte, Marina E. Perdigão, Adrie J.J. Straathof, Tim Van Winckel, Siegfried E. Vlaeminck
Due to climate change and increasing droughts, wastewater treatment and water reuse are gaining importance. Yet, the state-of-the-art bubble-aerated membrane bioreactor (BA-MBR) faces competitiveness challenges due to its high energy use and maintenance requirements, especially at small scale. This study investigates a novel membrane-aerated MBR (MA-MBR) that integrates membrane aeration and filtration to reduce energy consumption and system footprint, enabling resource-efficient non-potable reuse. The MA-MBR treated greywater for domestic reuse and achieved stable chemical oxygen demand (COD) removal efficiencies up to 95 % at high loading rates (up to 4 g L⁻¹ d⁻¹) and produced effluent with biological oxygen demand (BOD₅) values below 5 mg L⁻¹, meeting stringent reuse standards. Biomass dynamics revealed two distinct forms: biofilm on aeration membranes and flocs in suspension. Coarse bubble scouring facilitated biofilm detachment, enabling solid retention time (SRT) control. Oxidation-reduction potential (ORP) was linked to the biomass detachment efficiency, with negative ORP reducing mixed liquor suspended solids (MLSS) after scouring 5–10 times compared to operation at positive ORP. Reattachment of flocs reduced MLSS levels by 90 % within 60 min. A 25 % lower transmembrane pressure (TMP) in the MA-MBR compared to the BA-MBR after 72 h indicated lower fouling rates. Microbial communities were distinctly different between biofilm and flocs, especially under negative ORP conditions. These findings suggest the MA-MBR as low-footprint, low-fouling alternative for carbon removal from wastewaters with relatively high COD/N-ratios, and may improve resource efficiency for non-potable water reuse, for instance in decentralized source-separation applications. ...
BACKGROUND
2-Phenylethanol (2-PE) and 2-phenylethyl acetate (2-PEAc) are valuable aroma compounds with growing market demands. As an alternative to conventional petrochemical production, more valuable natural forms of these chemicals can be obtained by biotransformation. Low product concentrations, resulting from significant product toxicity to microorganisms, and high boiling points of products complicate recovery process. In situ product recovery by liquid–liquid extraction can be used to increase bioprocess yield and productivity. However, the subsequent purification of 2-PE and 2-PEAc is challenging as a consequence of the multiple phases, high-boiling temperatures of main products, occurrence of remaining substrate and byproducts, and presence of microorganisms.

RESULTS
The main goal of this original work is to improve the competitiveness of the biotechnological production of 2-PE by using in silico methods to develop an advanced industrial process for the final purification after centrifugation. An adaptable dividing-wall column was designed to remove 2-PE with 2-PEAc from organic phase or to esterify 2-PE to pure 2-PEAc. The production flexibility of the developed process allows adjustability to market demand. Additionally, recovery of co-produced ethanol from aqueous phase can increase the economic and environmental performance of the developed process. As confirmed by detailed techno-economic analysis, the proposed processes can cost-effectively (total recovery costs of 0.64–0.72 US$/kg2-PE/2-PEAc) and energy-efficiently (primary energy requirements of 1.83–2.05 kWthh/kg2-PE/2-PEAc) recovery of 2-PE or 2-PEAc after biotransformation.

CONCLUSION
The developed process enhances economic and environmental viability of biotechnological 2-PE production by reducing costs and energy requirements, while ensuring flexibility to adapt to market demands. ...
Many fermentation products inhibit their own microbial production, which complicates industrial-scale fermentation development for these products. When a product is volatile, this inhibition can be circumvented by removing product during fermentation through evaporation in a loop around the bioreactor. Microbes can survive this loop if its temperature is reduced using vacuum. Then, regrowing of microbes is not required. From a separation efficiency viewpoint, the evaporation loop should not use a single equilibrium stage, but a multistage vacuum distillation column. Such in situ product removal (ISPR) by vacuum distillation has hardly been recognized as an option, however. Costs for this product removal with subsequent purification are modest, even when product titers are low. A prerequisite is the use of advanced energy integration and heat pumping methods. ...
Journal article (2025) - Mungyu Lee, Ji Yeon Kim, Nulee Ji, Ludovic Jourdin, Adrie J.J. Straathof, In Seop Chang
Syngas fermentation is a promising bioprocessing method that utilises autotrophic organisms to convert C1 gases, such as CO and CO2, into valuable chemicals, offering both environmental and economic benefits. Despite these advantages, the industrial application of gas fermentation remains limited owing to challenges in productivity associated with gas substrates. While previous studies have focused on optimizing reactor design, mass transfer, and growth medium as solutions to these specific challenges, the direct correlation between cell viability and productivity remains unexplored. To address this gap, this study investigates the viability of the acetogenic strain Eubacterium callanderi KIST612 and its impact on acetate production across various operational modes. Unlike conventional single-reactor systems, a dual-reactor strategy was implemented to enhance viable cell retention, leading to improved process efficiency. This approach significantly increased the total carbon conversion rate to 9.30mmolh-1 and the specific productivity of viable cells to 0.13g gcell-1h-1, ultimately achieving the highest acetate titer (34.4gL-1) with >53% cell viability. These findings represent a major advancement over previous studies, demonstrating that maintaining cell viability is critical for optimizing acetate productivity. By integrating viability control into process operations, this study presents a scalable and efficient strategy to enhance gas fermentation performance, improve substrate conversion efficiency, and expand biochemical production potential for industrial applications. ...
BACKGROUND: 2-Phenylethanol (2PE) is a valuable aroma component that can be obtained through de-novo fermentation from glucose. However, its toxicity at very low concentrations (<2.5 g L−1) limits the fermentation titer, rate and yield. To address these limitations, in-situ product removal has been explored, leading to a recent scale-up to pilot scale. Nonetheless, an industrial scale has yet to be achieved. RESULTS: This original research pioneers conceptual development of two large-scale (2 ktonne2PE/y) production processes for 2PE via de-novo fermentation from glucose. Liquid–liquid extraction with oleyl alcohol and adsorption by hydrophobic resins followed by ethanol desorption, were alternatives considered for in-situ 2PE removal. For either design, solvent recovery and final purification were performed using advanced distillation techniques, including a heat pump-assisted distillation and a dividing-wall column. A fermentation titer of approximately 1.5 g2PE/Lbroth minimized production costs by achieving balance between upstream and downstream processing costs. This resulted in a cost-effective 2PE production for both designs of the recovery process (9.03–9.40 $/kg2PE). Sensitivity analysis revealed that glucose, oleyl alcohol, and ethanol costs strongly impact total production costs. CONCLUSION: This novel study provides a comprehensive and scalable process framework for the large-scale production of 2PE through de-novo fermentation. Integrating in-situ product removal and energy-efficient purification strategies, it marks a significant step forward in industrial biotechnology. ...

Model-Based Bioreactor Operation at Industrial Scale

Journal article (2025) - Eduardo Almeida Benalcázar, Wouter A. van Winden, Lars Puiman, John A. Posada, Mickel L.A. Jansen, Henk Noorman, Adrie J.J. Straathof
Alternative fermentation feedstocks such as ethanol can be produced from CO2 via electrocatalytic processes that coproduce O2. In this study, industrial-scale fermentation of ethanol with pure O2 for single cell protein (SCP) production was studied using a modeling approach. This approach considered (i) microbial kinetics, (ii) gas–liquid transfer, and (iii) an exploration of potential operational constraints. The technical feasibility for producing up to 58 kt/y of SCP in a 600 m3 bubble column operating in continuous mode was assessed and attributed mainly to a high O2 transfer rate of 1.1 mol/(kg h) through the use of pure O2. However, most of the pure O2 fed to the fermenter remains unconsumed due to the large gas flows needed to maximize mass transfer. In addition, biomass production may be hampered by high dissolved CO2 concentrations and by large heat production. The model estimates a microbial biomass concentration of 114 g/kg, with a yield on ethanol of 0.61 gx/gethanol (> 95% (Formula presented.)). Although the large predicted O2 transfer capacity seems technically feasible, it needs further experimental validation. The model structure allows the analysis of alternative substrates in the same way as identifying the best carbon feedstock. ...
Steel mill off gas fermentation presents a promising green alternative to petrochemical isopropyl alcohol (isopropanol, IPA) and acetone production while potentially reducing greenhouse gas emissions. A pilot-scale study stated negative global warming potential (GWP) at 85% gas conversion and 90% product selectivity. However, industrial-scale plant design including detailed techno-economic assessment (TEA) and life cycle assessment (LCA) remain undescribed. Therefore , this study modelled a heat-integrated 47.5 kton/ year gas fermentation process to IPA and acetone, based on pilot-scale data. The downstream processing was designed using vacuum distillation and heat-pump integrated (extractive) distillation to purify the 50 gproduct/ L broth with bi-omass and acetate as byproducts, to obtain 41.8 kton/ year of 99.6 wt. % IPA and 5.64 kton/ year of 99.0 wt. % acetone. Notably, no steam is consumed and 2.6 MWh of electricity is generated by utilising the energy from the steel mill off gas. The estimated unit production cost (UPC; 0.57 /kgproduct)issignificantlybelowmarketprices(1.65/ kgIPA and 1.45 $/ kgacetone). Moreover, the cradle-to-gate LCA gave GWPs of-1.42 kgCO2-eq/ kgIPA and-1.25 kgCO2-eq/ kgacetone, mainly due to avoided steel mill emissions. Other environmental impacts studied were also lower than for petrochemical production. Only the freshwater use is higher (70 L/ kgIPA and 62 L/ kgacetone) compared to petrochemical production (16 L/ kgIPA and 28 L/ kgacetone). Future research should study the impact of IPA and acetone selectivity and titer on the economic and environmental sustainability of steel mill off gas fermentation to IPA and acetone. ...

Modelling and Assessment of Syngas Fermentation at Different Titers and Yields

Abstract (2025) - G.J.A. Brouwer, T. Jankovic, Adrie J.J. Straathof, John A. Posada, A.A. Kiss
Journal article (2025) - Tamara Janković, Adrie J.J. Straathof, Siddhant Sharma, Anton A. Kiss
Fermentation can be used to obtain a wide variety of valuable high-boiling components. Among these components, microorganisms can produce aliphatic diols (e.g. propanediols, butanediols, etc.) in significant concentrations (e.g. 5–15 wt.%). Nonetheless, the high boiling points of these components, presence of microorganisms, and formation of by-products complicate recovery after fermentation. Hence, this perspective offers valuable insights into downstream processing options. A novel methodology was developed for recovering high-boiling components from dilute aqueous solutions, whereby both light and heavy impurities are present. The main steps in the proposed methodology are heat pump-assisted preconcentration and final purification in a dividing-wall column. These steps allow effective separation of high-purity product from water, light and heavy impurities. Furthermore, processes for recovery of 1,3-propanediol, 2,3-, 1,4- and 1,3-butanediol, designed according to the proposed methodology, were compared. Downstream processing performance is mainly determined by the product concentration in the fermentation broth, but is also influenced by the amount of impurities in the broth. ...
Isobutanol is a highly attractive renewable alternative to conventional fossil fuels, with superior fuel properties as compared to ethanol and 1-butanol. Even though the isobutanol production by fermentation has significant potential, complex downstream processing is limiting the wide-spreading of this technology. Accordingly, this original research significantly contributes to the advancement in industrial biofuel production by developing two eco-efficient downstream processes for the industrial-scale recovery of isobutanol (production capacity 50 ktonneIBUT/y), from a highly dilute fermentation broth (>98 wt% water). Vacuum distillation and a novel hybrid combination of gas stripping and vacuum evaporation were coupled with atmospheric azeotropic distillation to recover over 99.9 % of isobutanol as a high-purity product (100 wt%). Advanced heat pumping and heat integration techniques were further implemented to allow the complete electrification of these recovery processes. Furthermore, implementation of these techniques significantly decreased total annual costs (0.131–0.161 $/kgIBUT), reduced energy requirements (0.488–0.807 kWeh/kgIBUT) and lowered CO2 emissions (0.303–0.449 kgCO2/kgIBUT), resulting in highly competitive purification processes. In addition to efficiently recovering isobutanol, the designed downstream processes provide the potential to enhance the fermentation process by recycling all present microorganisms and reducing water demand. Therefore, the results of this original research substantially contribute to the advancement in industrial biotechnology and the wide-spreading of biofuel production. ...
Carbon-based products are essential to society, yet producing them from fossil fuels is unsustainable. Microorganisms have the ability to take up electrons from solid electrodes and convert carbon dioxide (CO2) to valuable carbon-based chemicals. However, higher productivities and energy efficiencies are needed to reach a viability that can make the technology transformative. Here, we show how a biofilm-based microbial porous cathode in a directed flow-through electrochemical system can continuously reduce CO2 to even-chain C2–C6 carboxylic acids over 248 days. We demonstrate a threefold higher biofilm concentration, volumetric current density, and productivity compared with the state of the art. Most notably, the volumetric productivity (VP) resembles those achieved in laboratory-scale and industrial syngas (CO-H2-CO2) fermentation and chain elongation fermentation. This work highlights key design parameters for efficient electricity-driven microbial CO2 reduction. There is need and room to improve the rates of electrode colonization and microbe-specific kinetics to scale up the technology. ...
Combining intermittent renewable electricity (IRE) with carbon capture and utilisation is urgently needed in the chemical sector. In this context, microbial electrosynthesis (MES) has gained attention. It can electrochemically produce hexanoic acid, a value-added chemical, from CO2. However, there is a lack of understanding regarding how the intermittency of renewable electricity could impact the design of a MES plant. We studied this using Aspen Plus models. A MES plant that was powered by constant grid electricity could operate from 100% down to 70% of its nominal capacity, at which point the heat exchangers and the internal geometrical design of the distillation towers became bottlenecks. The levelised production cost of hexanoic acid (LPCC6A) was estimated at 4.0 €/kg. Switching to IRE supply increased LPCC6A to 5.3 €/kg (for wind electricity) and 4.7 €/kg (for hybrid renewable electricity). A battery energy storage system (BESS) was deployed. The lowest LPCC6A was found at a BESS installation of 29 GJ/h for wind electricity (5.1 €/kg) and at 12 GJ/h for hybrid renewable electricity (4.7 €/kg). In both situations, the volume flexibility of the MES plant was not improved. At the investigated market and operating conditions, coupling IRE to the MES plant was economically infeasible. ...
Ethyl acetate is a platform chemical conventionally obtained through fossil fuel routes, but more recently its production by fermentation from carbohydrates has been scaled up to a pilot scale. Yet, the complexity of downstream processing (low product concentrations in liquid broth and in off-gas, azeotrope formation, and the presence of microorganisms) may complicate industrial application. This original theoretical study is the first to develop advanced downstream processing, based on process intensification principles, for large-scale recovery (~10 kton/year) of ethyl acetate after fermentation. To minimize product losses, ethyl acetate is separated from both the liquid broth and off-gas. The final purification is performed in a highly integrated azeotropic dividing-wall column. The economic and sustainability analysis shows that using refrigeration for initial product separation from the gas phase is more cost-effective (~0.61 $/kg) and less energy-intensive (2.20–2.40 kWthh/kg) than compression combined with high-pressure condensation using chilled water (1.09 $/kg and 9.98 kWthh/kg). ...
Even though industrial biotechnology is successfully used for the production of some chemicals, for many other chemicals it is not yet competitive with conventional petrochemical production. Usually, fermentation as well as downstream processing requires improvement. Downstream processing has to deal with low product concentrations, microorganisms, impurities and thermodynamic constraints (e.g., azeotropes), which often makes it very challenging and expensive, especially on a large scale. However, downstream processing of biochemicals has not attracted as much attention as upstream fermentation processes. In that context, this perspective paper offers a lightly referenced scholarly opinion about the downstream processing performance of different bioalcohols after fermentation. Due to the stronger toxicity effects on microbes, the achievable concentrations of monohydric aliphatic alcohols in the fermentation broth decrease with the increasing chain length. Specifically, the concentrations used here are 6.14, 5.00, 1.61 and 0.24 wt% of ethanol, isopropanol, isobutanol and hexanol, respectively. More dilute fermentation broths lead to more complex recovery processes. According to our previous work, the total purification costs increase from 0.080 USD kg−1 for ethanol, 0.109 USD kg−1 for isopropanol and 0.161 USD kg−1 for isobutanol to 0.529 USD kg−1 for hexanol. A similar trend is noticeable for the energy usage (0.960, 1.348, 2.018 and 3.069 kWthh kg−1, respectively) and the related CO2 emissions (0.164, 0.221, 0.449 and 0.555 kgCO2 kg−1, respectively). This work shows that advanced separation and purification based on process intensification principles are crucial for overall efficient production processes. The achievable product concentration in the fermentation broth – and not so much the alcohol chain length – has the biggest influence on the performance of downstream processing. Therefore, simultaneous development of both upstream and downstream processing is necessary to ensure the competitiveness and viability of industrial fermentation processes. © 2024 The Author(s). Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI). ...
Propionic acid is a valuable platform chemical that is usually produced via fossil routes. As these are energy-intensive and eco-unfriendly processes, fermentative production of propionic acid is becoming more attractive. However, the complex downstream processing (due to low achievable product concentrations, high water content, presence of by-products and thermodynamic constraints), presents a potential barrier to scale-up this technology. This original research proposes a novel intensified large-scale (production capacity of ∼ 20 ktonne/y) process for the final recovery of propionic acid after the initial biomass and counterion removal. Vacuum distillation steps ensure the recovery of a high-purity succinic acid product (>99.9 wt%) and a water stream that may be recycled to the fermentation to reduce the fresh water requirements. The main unit that follows is a highly integrated heat pump-assisted dividing-wall column (DWC), which allows the effective separation of propionic (>99.9 wt%) and acetic acid (99.4 wt%) products. Alternatively, it can serve as a reactive DWC that performs the esterification and separation of methyl propionate (99.8 wt%), methyl acetate (91.0 wt%) as higher added value products, and water by-product. If needed, extractive distillation can be implemented additionally to recover methyl acetate at higher purity (99.9 wt%). Overall, both options are proven to be economically interesting (recovery costs of 0.399 – 0.469 $/kg considering the product price of 1.349 – 1.802 $/kg) and environmentally attractive (3.206 – 3.678 kWthh/kg). ...
Microbial electrosynthesis (MES) is a novel carbon utilisation technology aiming to contribute to a circular economy by converting CO2 and renewable electricity into value-added chemicals. This study presents a cradle-to-gate life cycle assessment (LCA) of hexanoic acid (C6A) production using MES, comparing this production with alternative technologies. It also includes a cradle-to-grave LCA for potentially converting C6A into a neat sustainable aviation fuel (SAF). On a cradle-to-gate basis, MES-based C6A exhibits a carbon footprint at 5.5 t CO2eq/tC6A, similar to fermentation- and plant-based C6A. However, its direct land use is more than one order of magnitude lower than plant-based C6A. On a cradle-to-grave basis, MES-based neat SAF emits 325 g CO2eq/MJ neat SAF, which is significantly higher than the counterparts from currently certified routes and conventional petroleum-derived jet fuel. However, its negligible indirect land use change emissions might potentially make it competitive against neat SAFs originating from first-generation biomass. ...