CHITOSE’s strain development capabilities to meet industrial needs

#Strain Development　#Genetic Engineering　#Synthetic Biology　#Breeding　#AI　#Genetic Modification　#Algae Development　#Enzyme Engineering

In recent years, it has become possible to create microorganisms with desired functions directly through synthetic biology methods such as genetic engineering and genome editing. At the same time, the limitations of relying solely on these methods of strain development have become apparent. This is because synthetic biology methods are grounded in deductive approaches, and alone are insufficient when dealing with living organisms, which still have many unexplored and poorly understood aspects.
We have developed a unique strain development technology that combines synthetic biology methods with our proprietary disparity mutagenesis method to create strains with industrial-level performance, beyond research use.
Our strain development technologies can be applied in a variety of cases: for organisms where gene editing technologies are not available, for traits that could not be introduced by conventional breeding, or as whole-genome fine-tuning after gene editing to obtain strains better suited for production environments.

Background issues

In the development of industrial strains, synthetic biology methods are commonly employed. However, even with the most advanced technologies, optimization is limited to specific parts of an organism, making whole-cell optimization impossible and preventing the achievement of practical performance required for industrial use.
Advanced machine learning techniques are often used to optimize specific enzymes or metabolic pathways, for example, by training models on data obtained from wild-type enzyme sequence alignments of various species and comparative analyses between species. However, this approach still represents only a limited level of optimization, and the noise within the training data is often not adequately addressed. As a result, although production performance may improve compared to the wild strain, it still does not reach a practical industrial level.
Synthetic biology methods are limited in the traits they can target, and there are currently no practical technologies capable of optimizing the entire genome, such as for environmental adaptation or overall metabolic balance.

Our technologies

Designing genes using synthetic biology according to the intended purpose, and subsequently introducing them into microorganisms or cells at optimal expression levels.
Maximizing the performance of enzymes that act as metabolic bottlenecks, using only refined learning data, optimizing the sequence and activity.
Using disparity mutagenesis to construct diverse mutation libraries unattainable with conventional methods, enabling the introduction of traits that cannot be achieved through genetic engineering. It can also introduce genome-wide mutations that allow genome-level adjustments, providing an effective means to further optimize strains after genetic engineering.
Selecting targets with desired performance from diversified resources, such as sequences or mutant strains, using high-throughput screening.

Current status

We have been providing contract development services to a wide range of companies in the food, chemical, and pharmaceutical industries, both in Japan and overseas.
Since our founding, we have completed over 100 development projects, and in recent years, demand has been particularly increasing in the field of precision fermentation.

Locations

Japan, Asia, Europe

MessagePICK UP PERSON

Ojima Takumi

Chitose Laboratory Corp.
Tech & Biz Development Div.
Senior BioEngineer

Thanks to advances in synthetic biology, things once thought impossible, such as producing chemical raw materials using microorganisms, are now becoming achievable. However, unlike what we sometimes think, it’s not a simple process of gathering genomic data from databases, running computer simulations, and then creating an engineered organism that will obediently produce the desired compound in large quantities. Those who have actually tried doing it know that things rarely go exactly as planned. No matter the species, living organisms are far more complex and intricately structured than we humans imagine, and because there is still so much we don’t understand, we cannot yet design them completely rationally. Ideally, we would uncover all these unknowns, but that would take an enormous amount of time, making it an unrealistic goal.

That’s why we believe the key to working with living organisms is not “engineering only after fully understanding everything,” but rather “engineering even while many things remain unknown.”

Over time, organisms have adapted to their environments using the ability to evolve. By leveraging tools such as synthetic biology and breeding, we have refined our techniques that draw out this evolutionary potential to create organisms suitable for industrial use. Our experience includes constructing new metabolic pathways, improving key synthesis enzymes for specific products, enhancing productivity, modifying cell morphology to achieve favorable cultivation, and optimizing strains for specific culture conditions. We have successfully developed a wide variety of strains with diverse traits across many species.

In any bio-based manufacturing process, strain construction is the critical first step. With our technologies, we can help solve challenges in industrial strain development, whether you aim to construct a new microbial strain or improve the productivity of an existing one.