The challenges and opportunities of protein and peptide commercialisation

KTN’s Knowledge Transfer Manager for Synthetic Biology, Dana Heldt explores ‘directed evolution’ and profiles some UK companies working in this space.

In October 2018, the Royal Swedish Academy of Sciences awarded half of the 2018 Nobel Prize in Chemistry to Frances H. Arnold for her work on “directed evolution of enzymes.”
For many, this was seen as the first Nobel prize for Synthetic Biology. Arnold and her group at the California Institute of Technology have developed evolutionary protein design methods to generate valuable enzymes which do not yet exist in nature.

Enzymes have been around since life developed on Earth and have evolved ever since. They carry out crucial reactions, speeding up those chemical reactions which otherwise would take much longer. In nature, organisms and subsequently enzymes, have adapted to changing environmental conditions over millions of years. While evolution is a slow process, scientists around the world use synthetic biology tools to speed up the process and engineer proteins with novel functions and desired characteristics in the lab.

‘Directed evolution’ mimics the natural evolution process. Mutations are randomly introduced into DNA. Automation enables high throughput DNA assembly, producing a library of mutated genes, potentially generating thousands of enzyme variations ready to be screened for the desired features. One of the disadvantages, if there is no reliable high throughput method available, is that the screening process can be very time consuming.

In contrast, rational design and de novo design take a more considered approach, which requires knowledge about the protein sequence, structure and function. Using computer algorithms and bioinformatic tools, i.e protein modelling, the required sequential changes to obtain the desired functions and/or characteristics are predicted.

But it’s not only protein engineering that advances. Improvements in analysis technologies enables researchers to discover novel enzymes. Nowadays, genomic DNA analysis is faster and cheaper, generating a huge amount of data in a short period of time, enabling genome mining and the identification of valuable enzymes from underexploited organisms.

Related to enzymes but much smaller in size and structure are peptides. There has been lots of focus on the design and development of novel peptide in the past, especially in the medical sector and the search for novel antimicrobial agents and vaccines. But it’s not only the pharmaceutical industry focussing on these amino-acid based structures. Novel and improved enzymes and peptides are crucial for all sectors in Industrial Biotechnology. They find applications in the chemical sectors as well as food, materials and textiles.

There is clearly high demand and various UK companies occupy the space, determined to serve customers and solve the challenges associated with protein engineering.

A selection of companies working in this area are highlighted below. To find out about other companies in this area have a look at the Synbio Landscape tool or contact KTN’s Knowledge Transfer Manager for Synthetic Biology, Dana Heldt.

LabGenius

James Field of London-based protein engineering company, LabGenius says despite the huge value of engineered proteins, their development is limited by the human species’ incapability of fully grasping the complexity of biological systems.

‚ÄúWe think that the key to improving the protein engineering process is to break through this cognition barrier.” says James. ‚ÄúTo do this, we‚Äôre developing an empirical computation engine, called EVA, capable of designing, conducting and critically, learning from its own experiments. The learning aspect means that EVA gets continuously smarter as it unpicks the genetic design rules that underpin life. Ultimately, this approach will give us the ability to engineer proteins with both enhanced and entirely novel functionality.‚Äù

SyntheticGestalt

The processes that make drugs and chemicals is hugely expensive, energy demanding and involves using toxic heavy metal catalysts. But they needn’t be according to Guy Lewy who, along with a team of biochemists and engineers, started SyntheticGestalt to develop smart tools that discover and create superior enzymes for industrial applications.

“Nature is the ultimate chemist” he says. “But to unlock its full potential, we will need to collect and process data in new ways.”

The team are finding enzymes that not only catalyse tricky chemical reactions at great speed, but work best in a warm tub, without toxic chemicals, and without high pressures. Guy says these reactions can be made cheaper, quicker, and more environmentally friendly.

Biocatalysts Ltd

It is generally accepted that only a small fraction (1%) of all microorganisms can be grown in the laboratory, so the potential of 99% of the world’s microorganisms remain locked away. Biocatalysts Ltd have realised that they could utilise metagenomic techniques to take DNA sequences directly from environmental samples, avoiding the need to culture the organisms in the laboratory.

Their MetXtraTM bioinformatics platform, which was developed in collaboration with European Bioinformatics Institute (EMBL-EBI) and supported by Innovate UK, allows customers to access novel enzymes. Carolyn Pritchard says the platform “provides an intuitive enzyme discovery interface with Biocatalysts’ metagenomics libraries comprising over 335 million novel enzymes from a variety of metagenomes. 98% of our metagenome sequences are unique to our collection and not in the public domain, which means customers have access to novel enzymes that have previously been unobtainable.”

Zentraxa

“Synthetic peptides are notoriously difficult to manufacture due to their inherent complexity” says Zentraxa’s Harriet Bray. “Existing methods are financially and environmentally costly, and have to be optimised for each peptide sequence. This means many peptides cannot be economically produced.”

Zentraxa’s core technology circumvents this problem: it follows a bio-based approach allowing any peptide comprised of the 20 naturally occurring amino acids to be produced following one, universal process. This unrestricted access means that novel peptides can be designed-for-purpose, without having to consider production implications.

Zentraxa has already demonstrated its core peptide production technology on next generation adhesive peptides, resulting in superior flexibility, biocompatibility and biodegradability.

Thank you to following for their contributions:

James Field, LabGenius
Guy Lewy, SyntheticGestalt
Carolyn Pritchard, Biocatalysts
Harriet Bray, Zentraxa