Computational fluid dynamics simulation of an industrial P. chrysogenum fermentation with a coupled 9-pool metabolic model: Towards rational scale-down and design optimization

We assess the effect of substrate heterogeneity on the metabolic response of P. chrysogenum in industrial bioreactors via the coupling of a 9-pool metabolic model with Euler-Lagrange CFD simulations. In this work, we outline how this coupled hydrodynamic-metabolic modeling can be utilized in 5 steps. (1) A model response study with a fixed...

From industrial fermentor to CFD-guided downscaling: what have we learned?

Euler–Lagrange computational fluid dynamics simulations offer great potential for the integration of transport dynamics and metabolic dynamics in fermentation systems. Since the seminal work of Lapin et al. [1,2], progress has been made, mainly in the analysis of CFD data and translation to laboratory setup designs. Different large-scale...

Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition

Oxygen limitation is regarded as a useful strategy to improve enzyme production by mycelial fungus like Aspergillus niger. However, the intracellular metabolic response of A. niger to oxygen limitation is still obscure. To address this, the metabolism of A. niger was studied using multi-omics integrated analysis based on the latest GEMs ...

Biochemical engineering's grand adventure

Building on the recent revolution in molecular biology, enabling a wealth of bio-product innovations made from renewable feedstocks, the biotechnology field is in a transition phase to bring the products to the market. This requires a shift from natural sciences to engineering sciences with first conception of new, efficient large-scale...

Bioprocess scale-up/down as integrative enabling technology: from fluid mechanics to systems biology and beyond

Efficient optimization of microbial processes is a critical issue for achieving a number of sustainable development goals, considering the impact of microbial biotechnology in agrofood, environment, biopharmaceutical and chemical industries. Many of these applications require scale-up after proof of concept. However, the behaviour of...

Thermodynamics and economic feasibility of acetone production from syngas using the thermophilic production host Moorella thermoacetica

Background: Syngas fermentation is a promising option for the production of biocommodities due to its abundance and compatibility with anaerobic fermentation. Using thermophilic production strains in a syngas fermentation process allows recovery of products with low boiling point from the off-gas via condensation. Results: In this study we...

Euler-Lagrange analysis towards representative down-scaling of a 22 m3 aerobic S. cerevisiae fermentation

With reaction timescales equal to or shorter than the circulation time, the ideal mixing assumption typically does not hold for large scale bioreactors. As a consequence large scale gradients in extra-cellular conditions such as the substrate concentration exist, which may significantly impact the metabolism of micro-organisms and thereby the...

Lagrangian modeling of hydrodynamic–kinetic interactions in (bio)chemical reactors: Practical implementation and setup guidelines

Large substrate concentration gradients can exist in chemical or biochemical reactions, resulting from a large circulation time compared to the turnover time of substrates. The influence of such gradients on the microbial metabolism can significantly compromise optimal bioreactor performance. Lapin et al. (2004) proposed an Euler–Lagrange CFD...

Scale-up/Scale-down of microbial bioprocesses: a modern light on an old issue

The bio-economy is in transit from innovation to commercialization. The bioprocess industry is expected to increasingly deliver bio-products to the market, in large amounts, at high quality and at competitive cost levels. This requires flawless start-up of new large-scale bioprocesses and continuous improvement of running processes....

Euler-Lagrange computational fluid dynamics for (bio)reactor scale down: An analysis of organism lifelines

The trajectories, referred to as lifelines, of individual microorganisms in an industrial scale fermentor under substrate limiting conditions were studied using an Euler-Lagrange computational fluid dynamics approach. The metabolic response to substrate concentration variations along these lifelines provides deep insight in the dynamic...

Integrated isotope-assisted metabolomics and ¹³C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger

Background: Aspergillus niger is widely used for enzyme production and achievement of high enzyme production depends on the comprehensive understanding of cell's metabolic regulation mechanisms. Results: In this paper, we investigate the metabolic differences and regulation mechanisms between a high glucoamylase-producing strain A. niger...

Microbial Aldonolactone Formation and Hydrolysis - Kinetic and Bioenergetic Aspects

Methodology on monitoring and modelling of microbial metabolism