‘Recombinant protein’ might sound like a futuristic biotech term, especially when uttered in the same breath as the words ‘precision’ and ‘fermentation’, but in fact, we already use recombinant proteins in everyday life. They are often in the form of enzymes, which are proteins with a particular activity.
“The enzymes in our laundry detergents are recombinant proteins, as are the enzymes that are added to animal feed to make it more digestible, and the COVID vaccine was put together using seven different recombinant enzymes,” Josh Robinson, CEO of Cocoon Bioscience, told Fi Global Insights.
What’s more, recombinant proteins are already in widespread use in the food industry, as Cristina Corral-Ramos, applied microbiology scientist at Cultiply, points out.
“In the cheese industry, recombinant chymosin [rennet] is an enzyme used to induce curdling of milk. The brewing, wine, and baking industries use enzymes like amylases, glucanases, proteases, cellulases and glutenases that are produced by recombinant technology. Similarly, the dairy industry employs recombinant lactase to break down lactose, facilitating the production of lactose-free dairy products,” she said.
Recombinant proteins explained
So what are recombinant proteins and how are they different to normal proteins?
Corral-Ramos defines them as “molecules that are produced by introducing specific genes (DNA sequences) into an organism such as bacteria or yeast”.
“These genes have the necessary instructions for the host (the bacteria or yeast) to produce the desired enzyme or protein. The organism acts like a factory, producing a high amount of this protein of interest. This is possible using molecular tools,” she explained.
Asked how they differ to normal proteins, she replied: “Normal proteins are extracted by traditional methods directly from natural sources, such as plants or animal tissues. In contrast, recombinant proteins are produced using biotechnology in microorganisms like small protein factories in controlled environments.”
Animal-free improvements
Given the deep tech and investment involved in the development of recombinant proteins and the often complex regulatory approvals procedure they have to go through, it begs the question as to why companies bother with recombinant proteins when conventional proteins are so much more straightforward.
The answer to this lies in the opportunities that recombinant protein technology opens up.
“As well as giving us a way of avoiding killing lots of animals to extract what we need, recombinant proteins enable us to improve on what nature has already done,” said Robinson.
Corral-Ramos adds: “Some functions of recombinant proteins in industrial settings are to optimise processes, enhance qualities or replace animal-ingredient dependence.”
She lists four areas in which recombinant proteins offer an advantage over ‘normal’ proteins: customisability, purity, sustainability and scalability.
Expanding on what she means by ‘customisability’, she said: “By modifying DNA sequences or by selecting proper microorganisms we can adapt proteins to specific requirements. For example, increasing stability at high temperatures or, in the case of enzymes, optimising its activity under certain conditions.”
Recombinant production promotes purity by minimising impurities, allergens, and unwanted byproducts; it supports sustainability by reducing dependency on animal-derived or plant-intensive sources; and it enables scalability as the production process can be adjusted through adaptation of the genetic design or microorganism, said Corral-Ramos.
Chymosin is one example of how recombinant production decouples cheese consumption from the meat industry. Previously, rennet was extracted from animal stomachs.
Food technology startup Perfect Day’s process for producing whey protein via fermentation in microbiota is another example of how recombinant technology can reduce dependency on animal-based production.
Where does precision fermentation come into it?
Precision fermentation is a means of producing recombinant proteins, but it can also be used for producing other ingredients, such as flavourings. Likewise, recombinant proteins can be produced via other methods.
“Precision fermentation is used to produce general microorganisms using a bioreactor with a highly controlled environment, but it is also one of the methods used to produce recombinant proteins,” explained Corral-Ramos.
“Associated with recombinant protein, precision fermentation refers to using microbial hosts like yeast, bacteria or fungi to produce these molecules in a controlled environment using a bioreactor.”
Barriers to wider use
Cultiply has identified three main barriers to the wider use of recombinant proteins: regulatory hurdles, consumer perceptions and the cost of development.
Whilst the enzymes themselves are often free of genetic material, the microorganisms producing them may be classed as GMOs.
“This means that the recombinant protein may be incorporated into food as long as it does not contain any traces of the producer microorganism,” said Corral-Ram.
She believes that transparent communication and education on scientific advancements are the keys to overcoming consumer scepticism, and says that technological advances are helping companies in this space to overcome the historically prohibitive R&D and scaling costs, making more projects viable.