Robust cell factories can promote sustainable bioproduction

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Luca Torello Pianale
Luca Torello Pianale.

Yeast cells and other microorganisms can be used for sustainable industrial production of valuable biomolecules. However, when these so-called cell factories are used in large-scale processes, they are subjected to conditions that can affect their performance. Researchers at Chalmers University of Technology are developing tools that can lead to more efficient and stable cell factories.

Yeast cells can ferment biomass substrates, such as by-products from the forestry industry. In the process, the yeast cells, also referred to as cell factories, can be engineered to convert the biomass into valuable products such as biofuels, biochemicals, and pharmaceuticals.

However, there are several challenges that yeast and other microorganisms face when grown in industrial large-scale reactors, such as presence of gradients within the reactor of several parameters, occurrence of mutations and contaminations or, in general, environments that microorganisms are not evolved to live in. Furthermore, bioprocesses must be cost-efficient and scalable to compete with conventional production methods, such as fossil fuel production.

Better understandning for robustness features

Luca Torello Pianale, researcher at the Division of Industrial Biotechnology, recently defended his doctoral thesis on tools and applications to assess yeast physiology and robustness in bioprocesses. Robustness is defined as the ability of a system to maintain a stable performance despite perturbations in the environment.

Yeast strains selected for production may perform well in laboratory conditions. However, when exposed to large scale industrial environments, cells are exposed to conditions that may negatively impact efficiency. A better understanding behind robustness features in yeast may be crucial for the profitability of the production.

"For the industry, it might be more cost-efficient to find a robust and stable strain to begin with and then try to genetically engineer it to perform and produce well – instead of choosing a strain that is efficient but not throughout the fluctuating conditions of the process," says Luca Torello Pianale.

Robustness quantification

When evaluating how different conditions, such as various inhibitors in the lignocellulosic hydrolysates (the treated plant biomass used for second-generation biofuel production), affect the growth and metabolism of cell factories, researchers typically test the different inhibitors one by one, or a few at a time. This method is unlikely to reflect the complex conditions in which cells grow during industrial production. However, Luca Torello Pianale and his colleagues in the Division of Industrial Biotechnology aim to change that.

In a recently published study, Luca Torello Pianale presented four ways to implement robustness quantification while investigating cell factories. One laboratory strain of Saccharomyces cerevisiae (baker's yeast) and two industrial strains were cultured in seven different lignocellulosic hydrolysates. Using fluorescent biosensors, the researchers analysed the three strains based on several growth-related functions, such as specific growth rate and product yield, as well as eight intracellular parameters.

The advantage of using of fluorescent biosensors in this analysis relies on the ability to quickly assess how different parameters are changing over time without the need of other instrumentation or further analysis, reaching a level of monitoring that is almost real-time.

“Being able to grasp such information early on in the strain development and improvement pipeline would give new insights and depth to the analysis of strains used for industrial purposes,” says Luca Torello Pianale.

"Our tools can play a crucial role"

In the study, the versatility of the robustness quantification formula previously developed by Cecilia Trivellin, PhD student in the same research group, allowed to explore very different aspects of function stability, such as being able to assess the degree of stability over time of functions and population heterogeneity, phenomenon causing many problems in bioindustries

"I believe our tools can be very useful in an industrial context, ensuring consistent performance regardless of the perturbations or conditions you put them in, such as different substrate types. Our tools can play a crucial role in advancing towards a sustainable green bioeconomy," says Luca Torello Pianale.

 

More about the research

Author

Susanne Nilsson Lindh