Evolva has four significant technology capabilities, all associated with getting yeast to make valuable products
Combinatorial Genetics. Evolva can create billions of different yeast cells expressing multiple new gene combinations.
We have an array of technologies that allow us to rapidly insert and express 10s to 100s of genes in billions of individual yeast cells in a highly combinatorial fashion. This allows us to explore large numbers of gene combinations and hence find those gene combinations that are necessary to make (biosynthesise) a given ingredient. It also allows us to find those gene combinations that give the highest production rate (and hence the lowest production cost). The same approach can create novel pathways that generate diverse small molecules for drug discovery and similar activities. The genes that we use are either sourced (in compliance with the CBD) from various species or constructed de novo based on online databases or other sequence data
Screening and Analytical Technologies. Evolva has an array of advanced screening tools that can select those yeast cells that produce desirable ingredients from a background of large number of cells.
We have both function-led and structure-led screening tools that allow us to rapidly identify which yeasts are making desired ingredients and/or which have acquired desired functions (as a result of making certain ingredients).
- Function-led screens are typically based on fluorescence- or survival-based read-outs and have throughputs of up to 1 billion screening events per day. We have used such screens to discover novel molecules with potential utility against cancer and infectious disease, amongst others. The approach can also be used to find new functionalities for food ingredients.
- Structure-led screens use state-of-the-art capabilities that combine ultra-high performance liquid chromatography with time of flight mass-spectroscopy, NMR and a large internal database for the identification. They are primarily used to elaborate production pathways for known ingredients.
Pathway Optimisation Technologies. Evolva has a number of tools that can improve the efficiency with which yeast produces the desired product, which results in a lower cost as well as other benefits.
Once a biosynthetic route has been established, it is important to improve it with respect to purity of product, yield, speed of conversion and final titre. The more these elements are optimised, the lower the cost of production of the ingredient. In addition to our combinatorial genetics approach, one important tool is the ability to simultaneously insert (and test) multiple (>10) genes into the yeast genome. We also optimize pathways using a combination of molecular engineering, enzyme co-factor balancing, metabolic engineering and pathway flux analysis.
Decoration Technologies. Evolva has proprietary technologies that allow it to enhance the properties of ingredients, as well as their economics.
We have multiple collections of enzymes that allow us to “decorate” ingredients and hence enhance their properties. One particular focus is glycosylation (the process of attaching glucose or other sugars to molecules). Glycosylation allows us to:
- Make ingredients (such as stevia and saffron) whose natural properties depend on their glycosylation patterns.
- Improve the bioavailability of certain molecules, hence improving their effectiveness in nutritional or pharmaceutical use (or allowing a reduced amount of the relevant molecule to have the same effect as the larger amount).
- Improve manufacturing efficiencies by orders of magnitude, resulting in reductions in the relevant ingredient’s manufacturing cost.
Other decoration technologies allow us to functionalise molecules for further chemical derivatisation, alter lipophilicity or stability, etc.
Explain more about the benefits
This paper describes the “Discovery and Reconstitution of the Cycloclavine Biosynthetic Pathway” and demonstrates the potential for producing complex fungal alkaloids by fermentation in yeast.
The important ergot alkaloid intermediate chanoclavine-I produced in the yeast Saccharomyces cerevisiae by the combined action of EasC and EasE from Aspergillus japonicus
Yeast Synthetic Biology Platform Generates Novel Chemical Structures as Scaffolds for Drug Discovery. This documents the “chemical space” that is created by Evolva’s platform - diverse low molecular weight compounds with a high degree of novelty compared to both synthetic and natural product scaffolds.
Reconstruction in yeast of a fungal polyketide pathway, for production of the natural pigment rubrofusarin. Provides a rare example of successful expression in yeast of a large iterative non-reducing polyketide synthase.
Article about Evolva’s Technology. Yeast artificial chromosomes employed for random assembly of biosynthetic pathways and production of diverse compounds in Saccharomyces cerevisiae
Heterologous pathways for biosynthesis of vanillin from glucose established in fission yeast and baker’s yeast. The Article for free download.
Altered substrate specificities of family 1 UDP-glycosyltransferases gained by swapping of enzyme domains. The abstract of the Article.
Introductory overview article on Evolva technology in German language. Article can be downloaded here.