Biofoundries speed up the discovery of novel yeasts and bacteria of interest

Unlike what the name may suggest, biofoundries have nothing to do with molten metal. Instead, we are presented with a resolutely modern and sterile environment, where dozens of robots and lab instruments perform coordinated tasks to carry out all the procedures required for DNA sequencing, genome editing or the selection of micro-organisms. Yet there is a specific reason behind that name: just like foundries have transformed the metal industry in the 19^th century, biofoundries, also known as genetic foundries, genome foundries or DNA foundries, are a true technological breakthrough. A biofoundry allows scientists to program cells on a high-throughput scale, opening up new development opportunities for the yeast and fermentation industry.

From synthetic biology to biofoundries

Today, twenty-six prestigious academic institutions, including Harvard University and Imperial College London, have set up biofoundries. The development of these facilities fits within a larger trend, namely, a real interest for metabolic engineering. This method is used to better understand the functioning of living organisms and/or develop within a laboratory biological systems with desired properties, e.g. yeast or bacteria cells capable of naturally synthesizing a molecule of therapeutic interest. While initial research on designing biology dates back to almost twenty years ago, the year 2010 marks the birth of this discipline. A team from the J. Craig Venter Institute (JCVI) found a way to build a perfectly functional bacterial genome from scratch, paving the way for new industrial micro-organisms. While it made it possible to engineer new microbial strains based on needs, it also offered the opportunity to create “tailor-made living factories” able to synthesize – by fermentation instead of chemically – medicines and biofuels, as well as compounds, such as isoprene, used for the manufacture of petroleum-free polymers.

Designed for making targeted and specific changes to DNA sequences, and sometimes engineering synthetic genes or genomes, gene editing technologies have been constantly improving for the past ten years. Significant progress has also been made in other fields, such as rapid cell sorting (by flow cytometry), automation, robotics, IT storage capacity and data science. All these innovations combined now make it possible to use computer-aided design, achieve rapid sequencing of large amounts of synthetic DNA, and have different gene combinations analysed and tested simultaneously.

Biofoundries: accelerators of innovation

Bioengineering processes – pipetting very small quantities of liquids, introducing genetic material into cells, screening engineered micro-organisms, etc. – have always required a high level of precision, meaning they were very time-consuming. By automating and systematizing these laborious processes, biofoundries significantly accelerate and improve the accuracy of R&I cycles, from the engineering of a new strain of yeast to production and verification of the result. Most importantly, they also provide the opportunity to design and test thousands of microbial prototypes at the same time. A robotic arm transfers small plastic trays with thousands of tiny wells and as many samples from one instrument to another. After creating genetic variation across hundreds of thousands of variants of yeast and bacterial strains, all these options can be assessed simultaneously using automated protocols and data analysis software in order to select the best models.

Biofoundries can also contribute to the development of non-genetically modified organisms (e.g. in food products), since all the stages that help with the selection and crossbreeding of yeast cells, through a directed-evolution approach, can be automated as well. Even when more traditional methods are used, they facilitate the rapid creation of the strains. This is particularly important for Lesaffre given its commitment not to use genetically modified organisms for food and feed applications.

New discoveries in the pipeline for Lesaffre

The biofoundry which will open in the Autumn will be equipped with 14+ robots, more than 30 state-of-the-art instruments, and design and data analysis software, including a stereolythograpic 3D printer per labware prototyping. The facility will also bring together three types of expertise: specialists in automation and software engineering, high-throughput screening researchers and biological engineering experts (an eclectic mix of classical yeast breeders, genetic engineers, metabolic engineers, microbial physiologists, and system biologists). It will particularly benefit from state-of-the-art gene editing technology, especially after Lesaffre signed a strategic partnership with Recombia Biosciences in October 2020. This technology can be used to introduce multiple genetic changes at the same time, therefore generating thousands of different strains of yeast simultaneously. This should considerably expand the catalogue of bio-based ingredients which have been synthesized by genetically-reprogrammed yeast cells, e.g. biofuel compounds, substitutes for petroleum used in the manufacture of plastic materials, molecules of therapeutic interest, pesticide-free biocontrol products used for farming, etc, as well as significantly accelerate classical yeast and bacteria genetic improvement programs.

All our Business Units should see an advantage in working with the new biofoundry, including our bakers, brewers and oenologists: while these food sectors are limited to traditional development techniques, without access to genome editing, the new facility can screen thousand of yeast cells at the same time, increasing the chances of finding strains of interest in no time, i.e. which are more efficient in fermentation, create new flavours and generate a low level of fermentation by-products. These are exciting prospects. With a large number of possibilities, some of the gene combinations that will be tested might even lead to the creation of novel products or applications never introduced on the market before, which will respond to actual needs.