An enzyme engineered version of BRAIN Biotech´s CRISPR-BMC with superior properties in yeasts accelerates development of high-performance strains.
Yeasts are the unsung heroes of biotechnology. They have been used to ferment beer, wine, and bread for thousands of years but also serve as production organisms for enzymes, vitamins, and flavors. However, optimizing yeast strains has traditionally been a slow and challenging process. Classical breeding and strain improvement methods as well as conventional genetic engineering approaches often reach their limits in terms of specificity and timelines.
With the development of its CRISPR-BMC technology, BRAIN Biotech has taken a decisive step forward. The CRISPR-BMC (BMC = BRAIN Metagenomic Cas) system was discovered through BRAIN Biotech’s MetXtra platform for enzyme discovery and subsequently optimized for efficient use in yeast. Unlike conventional methods, CRISPR-BMC enables marker-free, highly precise genome editing, in a single step – including multiplexing.
While laboratory strains like Saccharomyces cerevisiae S288c were easily editable, robust industrial yeasts proved resistant. Our initial CRISPR-BMC gene scissors were simply “too blunt” for these strains.
Better interaction between the BMC nuclease and the genomic DNA, as well as balanced expression of the Cas enzyme and its guiding RNA molecule, were required.
The solution lays in enzyme engineering and molecular biological fine-tuning. By introducing specific amino acid modifications into the nuclease’s active site for better DNA binding, stabilizing the guide RNA in the cell, and using a carefully designed plasmid vehicle for transformation, the activity of the CRISPR-BMC system was significantly enhanced. The result is that the optimized variants of CRISPR-BMC achieve editing efficiencies of over 95 % in industrial yeasts.
This breakthrough opens new opportunities for various industries, including food and beverages, bioethanol, and the biosynthesis of natural compounds. By providing state-of-the art technology for engineering robust strains of Saccharomyces cerevisiae, development times can be significantly shortened. And this is just the beginning: The technology is not limited to Saccharomyces; it also works with other industrially relevant yeast, such as Torulaspora delbrueckii and Komagataella phaffii (Pichia pastoris).
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Combining our deep knowledge of CRISPR-BMC and rational enzyme engineering allows us to deliver solutions that bring speed and precision to strain development.
- Head of Microbial Strain Development
