Cell culture fermentation basics of investing

We examine why its the alternative protein sector to watch. The companies Precision fermentation companies have proliferated over the past decade, with investment accelerating over the last three years. Companies working on more niche product segments are also springing up.

Melibio, which makes bee-free honey, was founded in Qoa is one of the most innovative early start-ups. They have created chocolate that does not use any harvested cocoa. What is it? This is a biotechnology that seems almost too good to be true. The results are indistinguishable from farmed food, except they are not taken from slaughtered livestock. Precision fermentation is a form of cellular agriculture, a wider family of lab-based food production techniques that circumvent the need for livestock.

It is an outgrowth of traditional fermentation, a biotechnology as old as the hills. Beer and bread have been made through traditional fermentation as far back as ancient Mesopotamia and Egypt. Traditional fermentation is a relatively untargeted process. Microorganisms like bacteria or yeast simply break down complex molecules in organic matter into simpler ones. A newer strand of fermentation is biomass fermentation. Here, microorganisms themselves are cultivated for their protein content.

Established alternative protein companies like Quorn use this technique. Precision fermentation is different from traditional fermentation and biomass fermentation because it makes targeted use of microorganisms. In this technique, protein is no longer harvested from the bodies of the microorganisms themselves.

Instead, they are used as replicating machines. First, a fragment of DNA from plants or animals is selected for target properties. This DNA is then planted into a host microorganism — yeast, bacteria, or fungi. The host microorganism replicates the foreign DNA, producing large amounts of protein with desirable properties. The final step is purification, where the protein is extracted from the microorganism and processed into the final food product.

Adjusting the properties, flavour profile, and growth rate of fermented foods involves altering microorganism characteristics or the kinds of foreign DNA planted into them. This can be achieved through careful strain selection or genetic modification. Why precision fermentation? The ethical, health, and environmental advantages of lab-based agriculture are drawing investors and entrepreneurs. First of all, it promises reduced carbon emissions and land use compared to conventional agriculture.

However, not all these ingredients are easily sourced at large volumes and low prices. By using microbial cells as the production host, precision fermentation allows for highly scalable manufacture of virtually any ingredient. Target selection and design is the starting point for the process of precision fermentation.

The molecule or molecules of interest are referred to as the target. The target can be a protein, a lipid, a flavor compound, a fragrance, an enzyme, a growth factor, a pigment, or another class of molecule. Fermentation-derived ingredients are already widely used across the food industry. The majority of vitamins in nutritional supplements and fortified processed foods, such as B12 and riboflavin, are produced through fermentation, as are many flavoring components. The food industry was among the first to leverage fermentation to displace animal products in everyday use.

Other recombinant proteins, such as casein and whey, are key targets because of their unique functionality in dairy products. These proteins can be combined with plant-derived ingredients to create a final product. Precision fermentation targets specific molecules.

Target molecules such as animal-origin-free growth factors are used in the production of cultivated meat. Furthermore, proteins such as collagen or fibronectin produced through fermentation may serve as key animal-free components of scaffolding for more complex, highly-structured cultivated meat products. Depending on the target, both engineered and non-engineered approaches may be possible.

For example, the soy leghemoglobin protein produced by Impossible Foods is engineered into a yeast host strain for efficient, scalable production. On the other hand, microalgae company Triton Algae Innovations is commercializing heme proteins that are native to their algal strains, so no engineering is involved.

Instead, the genome encodes a series of enzymes that compose the biosynthetic pathway for producing the target molecules. For example, the target molecules for algal omega-3 production are the fatty acids DHA and EPA, but the instruction manual for manufacturing these fatty acids consists of several gene-encoded enzymes that convert precursor fatty acids into these desirable fatty acids within the cell.

As with protein targets, molecules like fats or flavoring molecules can be produced in microbial hosts either with or without the use of engineering techniques, depending on the specific target and the choice of host organism. Challenges in target selection for precision fermentation One of the most basic challenges for target selection is simply determining which molecules contribute the most to specific properties of animal products.

A litany of volatile compounds, many of which differ by species type and cut, contribute to the taste of different kinds of meat. Mass-producing already-existing molecules In many cases, several variants of a candidate target may already exist in nature. For example, almost every living organism contains heme proteins of some sort, but which ones perform the best as flavor enhancers for meat products?

Which are the most stable — not only during their production, but also through the downstream processing of the final food product and throughout its shelf life? Which target accumulates at the highest titers within host cells, thus allowing for the most favorable economics?

All of these answers must be ascertained through a combination of thorough empirical screening and predictive approaches. For target molecules that are not proteins, there are additional challenges: identifying biosynthetic pathways that can manufacture these molecules, and then determining whether these pathways already exist in suitable host organisms or if they must be engineered or enhanced for higher productivity.

For example, fermentation-derived lipid production is relatively unexplored for food applications but has a fairly robust history for industrial chemicals. The alternative protein industry may be able to develop an open-access research foundation and accelerate the commercialization of fermentation-derived fats by aggregating lipid synthesis pathway insights from the chemicals industry.

Each of these aspects feed into one of the key challenges within precision fermentation: improving the economics of production. To compete with animal-based proteins, researchers and companies must increase the titer amount of an expressed target molecule relative to the volume of total upstream-produced liquid containing the agent — the primary benchmark of upstream efficiency and yield the ratio of the mass of final purified protein relative to its mass at the start of purification — the primary benchmark of downstream efficiency of target molecules and protein biomass.

While strain development and feedstock optimization can contribute substantially to the overall economics, the target selection is a critical factor in achieving economic viability.

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