Recombinant protein production in microbes

Recombinant proteins are widely used in life-saving medicines, with recombinant insulin being one of the biggest success stories. Recently, the use of recombinant proteins in food has been gaining traction. Read this new post by Swati Choudhary (Shiru's Head of Strain Engineering) to learn more about how we're using Flourish™, our cutting-edge ingredient Discovery platform, to identify and create novel recombinant proteins and why we think it's important to utilize this technology for creating a sustainable food system.

Technology
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4
 Min read
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March 24, 2022

Over the past few decades, human beings have made huge strides in understanding biological systems. Today, we can select proteins of interest from any organism and express them in a different species that are easier to work with. Proteins produced in this manner are called recombinant proteins, and microorganisms are a preferred set of hosts for expressing recombinant proteins at an industrial scale. At Shiru, we use Flourish™, our cutting-edge ingredient discovery platform, to identify and create novel recombinant proteins whose functional properties make them superior and sustainable ingredients for the food industry. 

The path to a recombinant protein begins with DNA. A DNA sequence corresponding to the protein of interest is inserted into the host microbe with the help of sophisticated molecular biology tools. The resulting recombinant microbial strains are put through their paces - carefully monitored for productivity and ability to thrive under fermentation conditions. The recombinant protein may be intracellular, in which case the microbial cell is broken open to extract the protein. Or the microbe may secrete the recombinant protein, which is then purified from the culture media. Out of hundreds of recombinant microbial strains that Shiru evaluates through High-Throughput Screening (HTS), a select few graduate to larger fermentation tanks, and in the end, only one strain may make it to the ribbon at the finish line for commercial-scale precision fermentation.

Recombinant proteins are widely used today in food and medicine. The production of human insulin in microbes - developed by Genentech and brought to the market by Eli Lilly in 1982 - was an early indicator of the power of recombinant proteins [1]. In the treatment of insulin-dependent diabetes, recombinant insulin, produced via precision fermentation, has superseded native insulin sourced from pigs and cattle. Fermentation-produced chymosin, a key component of rennet, is another example of an animal protein that is produced industrially through microbes. In fact, fermentation-produced chymosin accounts for more than 90% of the rennet used in cheese production today [2].  The EVERY Company’s functional egg protein and Perfect Day’s milk protein are also recombinant proteins made via microbial fermentation. Shiru uses this same approach to provide highly functional ingredients to the entire food industry.

At Shiru, we are exploring nature’s diversity to identify proteins with food functional properties and bring them to the market. Recombinant plant proteins which are capable of promoting gelation, for example, can give structure to alt-meat patties and to non-dairy ice cream. Recombinantly expressing a food-functional protein has several advantages over purifying it from its native plant source. Compared to traditional farming methods, microbial fermentation needs less space, energy, and nutritional ingredients, and purification of the target protein can be much less labor-intensive [3]. Another advantage is the quality of the protein produced: proteins in almost all commercial isolates/concentrates from plants are denatured due to harsh processing methods, meaning that it is very difficult to do technically challenging things like making great plant-based cheeses that melt and stretch, for example. Additionally, microbes grow very quickly, and deliver target proteins within hours, compared to the months-long wait for plants to hit the “right” age when they produce the protein of interest. 

In short, recombinant proteins reduce the impact of food production on fragile ecosystems, while providing us with access to the incredible diversity that exists in nature and presents itself as new tastes and textures for all kinds of food products. As Shiru creates the next generation of sustainable ingredients, we will continue to leverage the power of recombinant protein production in microbes to deliver hero food ingredients with superior texture, taste, and sustainability attributes.

References:

  1. Baeshen, N.A., Baeshen, M.N., Sheikh, A. et al. Cell factories for insulin production. Microbial Cell Factories 13, 141 (2014). https://doi.org/10.1186/s12934-014-0141-0
  2. Johnson, M.E. A 100-Year Review: Cheese production and quality. Journal of Dairy Science 100:9952-9965 (2017). https://doi.org/10.3168/jds.2017-12979
  3. https://www.foodnavigator-usa.com/Article/2020/09/18/Microbes-the-third-pillar-in-the-alternative-protein-industry-The-rationale-is-simple-Fermentation-is-just-more-efficient

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