Study of the influence of mixing on the morphology and production of fumaric acid in Rhizopus oryzae using a scale-down approach

Status

Open

Scientific disciplines

Biosciences and Biotechnologies

Research direction

Catalysis, Biocatalysis and Separation

Affiliate site

Rueil-Malmaison

In order to reduce the environmental impact of transport and the chemical industry, IFPEN is investing in biorefineries, biofuels and bio-based chemistry. Among the targets being explored, fumaric acid has the potential to become a platform molecule, providing access to various bio-based molecules.
With strong expertise in life sciences and engineering, the TBI laboratory combines fundamental and applied research in the fields of biotechnology and process engineering to address the challenges of the bioeconomy.
Together with four other partners, IFPEN and TBI are participating in the BioFUMAC collaborative project, which aims to develop a new route to bio-based acrylic acid via robust bioproduction of fumaric acid through fermentation of the filamentous fungus Rhizopus oryzae. The BioFUMAC project is structured into three Work Packages: WP1 optimises and secures the production of fumaric acid; WP2 develops a new enzyme for the bioconversion of fumaric acid into acrylic acid; WP3 prepares the integration of these two steps into the overall process, including a nanofiltration step.
Despite very good production performance in the laboratory, there is currently no industrial-scale bioproduction of fumaric acid. Rhizopus strains can adopt various morphologies: free mycelium, pellets, aggregates, and the difficulty in controlling a particular morphological type is one of the barriers to scaling up.
The aim of this thesis is to validate the scale-up of the protocol for the production of fumaric acid by Rhizopus oryzae. It will draw on IFPEN’s experience in scaling up the protocol for the production of cellulases by Trichoderma reesei. It will also draw on TBI’s expertise in the study and modelling of interactions between hydrodynamics and biology in bioreactors.
Within the BioFUMAC project, this work will also draw on the results of an ongoing PhD thesis on the experimental optimisation of culture under ideal mixing conditions, which will enable the identification of optimal parameters in terms of, for example, temperature, pH, agitation, culture medium composition, etc.
Thus, in the first part (fermentation technology, led by IFPEN Rueil), we will use a two-stage fermentation setup allowing a ‘scale-down’ approach to reproduce in the laboratory the mixing conditions expected at industrial scale, in terms of power dissipation, shear and nutrient heterogeneities. We will then measure the impact of these non-ideal mixing conditions on the morphology of Rhizopus and on its fumaric acid production performance.
In a second phase (bioprocess modelling, led by TBI), we will combine all the data generated to construct an in silico model of a large-scale industrial bioreactor, integrating descriptions of hydrodynamics, gas-liquid mass transfer and biological reactions. This digital twin will enable us to quantify the loss of performance due to large-scale cultivation, thereby ensuring the reliability of the production protocol’s scale-up.

Keywords: fermentation technology, filamentous fungus, scale-up, scale-down, CFD modelling, bioreactor modelling

  • IFPEN supervisor    Dr. Etienne JOURDIER, ORCID : 0000-0003-3502-2982
  • TBI supervisor    Pr. Jérôme MORCHAIN, morchain@insa-toulouse.fr, ORCID: 0000-0002-3343-5655
  • Doctoral School    ED581 ABIES, AgroParisTech, Université Paris Saclay
  • PhD location  IFPEN, Rueil-Malmaison, France; A stay is planned for the second part of the PhD at TBI, INSA Toulouse, France.
  • Duration and start date    3 years, starting in Novembre 2026
  • Employer    IFP Energies nouvelles
  • Funding    Projet BioFUMAC, PEPR B-BEST
  • Academic requirements    University Master degree in biotechnology and bioprocess   
  • Language requirements    English level B2 (CEFR)    
  • Other requirements    Experience in fermentation technology, knowledge of bioprocess modelling, good communication and teamwork skills.

To apply, please send your cover letter and CV to the IFPEN supervisor indicated here below.

Contact
Encadrant IFPEN :
Dr. Etienne JOURDIER