Bioinformatics

Bioinformatics is an enabling tool used across project design and development at Isomerase.  Bioinformatics services can also be the focus of an entire project, such as genome sequencing and identification of an enzyme, or discovery of a biosynthetic gene cluster. We also write and develop our own proprietary software, such as EVOSELECT, a tool to support the directed evolution of enzymes.

From project inception, Isomerase uses bioinformatics to assess the potential of bacteria and fungi from both our own extensive culture collection and public collections, for their ability to produce compounds and proteins of interest to our innovation partners. This information is used alongside our extensive knowledge in working with these strains to allow us to engineer analogues, improve processes, optimise titres, and select ‘best-fit’ heterologous expression and production strains.

What is bioinformatics?

Bioinformatics is the science of analyzing large amounts of biological information via the application of computer science and information technology. It is particularly relevant in the fields of genomics and molecular biology, where bioinformatics can assess large amounts of genomic data (such as the genome of an organism that produces a valuable enzyme) and help find the gene sequence coding for the enzyme of interest. Bioinformatics can then be used to help design constructs to express this gene in a heterologous host, such as E. coli or Pichia.

How can a bioinformatics CRO like Isomerase support my projects?

Bioinformatics is a complex and rapidly evolving field. Isomerase bioinformaticians can use, generate and adapt software to help solve complex biological questions.  As a bioinformatics services provider, Isomerase has conducted a wide range of bioinformatics projects on behalf of partners. These can be standalone projects or support for existing or new projects. Examples include:

• Genome Analysis. Next-generation sequence assembly, annotation and analysis of prokaryotic and eukaryotic genomes for secondary metabolite production. This is especially important in identifying the biosynthetic pathway for novel compounds but also derivatives of known compounds with beneficial properties. It can be used alongside metabolic modelling to help predict strain and pathway engineering to improve the production of a metabolite of value.
• Genomics, proteomics and transcriptomics. Analysis of the genome of a series of bacterial and fungal strains to track down enzymes giving rise to particular biocatalytic activities. This can be based on literature prediction or known activity based on previous experimental data, for example, screening strain libraries from our biotransformation culture collection. If required, this can be followed by heterologous expression of the shortlisted enzymes and confirmation of activity in one or more host expression strains. The route can facilitate a vastly improved route to production, scale-up and reduction in cost of goods.
• Ligand binding modelling. Molecular modelling to predict the binding of a new ligand into an existing ligand-bound crystal structure, allowing the proposal of targets for enzyme engineering to swap the substrate of an enzyme.
• Genetic design. Bioinformatics services can support the design of expression cassettes for genes from vastly different genera to allow expression in a range of alternative strains with enhanced properties more suited to the industrial expression of the final product.
• Statistical design of experiments and process modelling – We frequently use JMP® software to design experiments to accelerate development towards an optimised process. The data collected is analyzed in JMP® to make predictive models to guide further R&D. These models can be used to identify process risk and allow troubleshooting, increase titres and be selected for other improvements to the process.

We can also run standalone consultancy projects as a bioinformatics CRO, where we can carry out in-silico analysis and generate reports for clients to assess potential projects before any lab work is initiated.

Why might Isomerase be the right bioinformatics CRO for my project?

The team at Isomerase not only has expertise in bioinformatics services but also extensive expertise in a range of other related subjects, including biosynthesis, enzyme engineering, genome sequencing and analysis, microbiology and synthetic biology. We are used to taking on complex bioinformatics projects and running them on behalf of partners in an open and collaborative way. This enables us to support partner projects with specific bioinformatics services as required, without them needing to hire staff, or access software or hardware themselves