PRODIGES

Winner of the 2024 call for projects.

The microbial bioproduction sector is a rapidly expanding field, producing a wide range of products for various market sectors, including pharmaceuticals, enzymes, chemicals, cosmetics and biofuels. Over its existence, bioproduction in biotechnology has relied on batch fermentation as the process of choices for many reasons (e.g. simplicity, shorter production time, good control over traceability, etc.). Nowadays, batch process is mostly selected « by default », as many contract manufacturers have accumulated a long experience and operational expertise and have pre-existing facilities that can be repurposed for different targets. Meanwhile, batch process is not exempt from flaws:

• Highly susceptible to demand-supply fluctuations.
• Difficulty to scale up.
• It generates a high footprint, as investment for batch facilities is important due to larger equipment size and immobilization, high operational cost for staff and consumables and expensive cleaning procedures.

As such, continuous bioproduction processes could be groundbreaking for biotechnological applications, answering some limitations of batch processes, and ultimately providing a more sustainable alternative. Continuous process can sustain a much higher theoretical volumetric productivity, with the promise of a more consistent product quality. However, the high initial development cost and times required to establish a continuous process has so far limit its appeal for biotechnological applications outside of the pharmaceutical sector. To de-risk the required investment and democratize continuous production, several factors and limitations needs to be answered,

• Genetic instability of the strain over a high number of cell generations
• Process control and real-time monitoring to ensure long-term operability and maintenance of sterility.

The PRODIGES project aims at de-risking continuous bioproduction processes by proposing PROcess-DrIven Genetic Engineering Strategies that will challenge the current production model. During the course of the project, a comprehensive study of the behavior of a microbial chassis cultivated in a continuous production mode will be carried, with the aim to propose strategies for ensuring stable and robust production of high-quality recombinant proteins combined with adapted downstream processing strategies.

The overall objectives of PRODIGES are:

• To construct and optimize two microbial cell factories for sustainable continuous production, with focus on genetic stability and secretion capacity.
• To assess continuous cultivation process, with focus on online monitoring, production stability, productivity and quality.
• To evaluate the gain of batch or continuous downstream processing operations.
• To provide a Techno-Economic Analysis and Life Cycle analysis, taking into account the constraints vs. process specifications and manufacturing costs in its experimental design.

This novel process driven development will create a game-changing rupture in the manner in which production hosts are designed for recombinant protein production, creating an innovation space to generate new IP leading to significant cost savings and accelerated development timelines.

To this aim, PROGIGES brings together an interdisciplinary consortium coming from the fields of molecular biology, microbiology and process system biology. The consortium is composed of 1 pre-industrial demonstrator certified by the french government (TWB-INRAE) and 2 academic partners (INP and INSA Toulouse).
 

Project lifetime:
 

2024 - 2028

Scientific manager:
 

Fayza Daboussi (INRAE)