Biotech basics in the battle for beef's bloodiness - Part I

Impossible vs Motif via GM yeast

• 2 June, 2022

This post summarises some biotech concepts and industry movements I’ve learned as a newcomer to the field. It’s intended to be narrative, notes and references that past-me would have found interesting and useful.

Impossible Meat mimetics

Impossible Foods' claim to fame is producing a plant-based burger product which has some of the unique characteristics of meat - taste, texture, colour and cooking behaviour. They have a patent which covers a realm of art, and they are particularly well known for their production of heme.

Heme is a family of molecules that provide the rich red colouring¹ in raw meat and denature at temperature, giving the satisfying experience of changing colour during cooking. Technically hemes are a subset of macrocycle tetrapyrolles, four pyrolles² arranged in a circular shape, combined with an iron ion. Taking their name from the Greek for blood, hemes are a precursor to hemoglobin, myoglobin and other similar proteins.

Heme derivatives are found in all plants and animals. Impossible Foods' heme is in the form of soy leghemoglobin, but they don’t harvest it from soy plants, rather they produce it using a process called precision fermentation.

Side note on precision fermentation

I find precision fermentation interesting enough to warrant its own tangent³. Here’s how Impossible brought blood to food without the meat.

First they identified the heme producing genes within the a soy genome, and genetically modified a particular strain of yeast⁴ to include those same genes, as well as a few other useful traits to increase overall productivity. The idea is that this genetically modified yeast, given the right conditions, will grow efficiently and then, when signalled, will express a target molucule - in this case soy leghemoglobin. Different organisms are differently able to express desirable molecules⁵, so the first win is when your yeast is expressing your target in the lab.

Alongside this genetically enhanced yeast is a matching precision fermentation plant. In the plant, the yeast is cultivated in bulk in a bioreactor and the signal for target expression is provided. Once done, the whole mass is passed through a fairly involved set of steps known as downstream processing⁶ to extract just the desired target.

It appears the ideal of being “more efficient than an animal” is not yet proven at scale. A precision fermentation plant is essentially a yeast factory, with the target molecule often making up <5% of the output volume. The process can theoretically be optimised at almost any point along the way, though each has its challenges - from the genetic engineering⁷ to the selection of yeast feedstock⁸, to expression signalling⁹, to the size and shape of the bioreactor¹⁰, and of course each step in the downstream processing. Achieving productivity at a scale that makes the business case stack up is the result of a complex dynamic system that is notoriously fickle. Being 1% less productive in output can mean losing 20% or more of your target.

For the last few decades precision fermentation has been used for high value target proteins such as vaccines and other pharmacological ingredients. With heme, Impossible Foods was fairly early to adopt the technique to create a food magic ingredient at scale.

More companies are adopting precision fermentation to produce high value food ingredients. One of the challenges is scaling up the process from the lab to hundreds of thousands of litres. On that front BioBrew have the largest ambitions, to create very large scale facilities, focussing on adaptive control systems that can break the current mould where plant desin and operation needs to be tightly coupled to its microbe, feedstock, media and target. If it comes to fruition, it will be a significant shift in the value chain to the industry, commodifying what has been custom to date¹¹.

A new Motif

Fast forward a few years and enter Motif Foodworks. Inspired by Impossible Foods and well backed, for example including by Bill Gates, they too have developed heme in the form of bovine myoglobin.

It’s a different heme molecule, derived from a calf muscle rather than from a soy root. They also use a precision fermentation process, modifying a yeast to express the bovine myoglobin. They launched last year with the level of fanfare expected from a well funded biotech startup. The launch was closely followed in March this year with a patent infringement case from Impossible Foods.

Naively I initially assumed that because the heme source was a different molecule from a different source then Motif should be in the clear, following Motif’s line that the two proteins are “fundamentally different, and deliver different flavour and aroma benefits”. But looking at Impossible’s patent, they cover “a beef substitute that uses a muscle replica including a heme-containing protein…" (among other ingredients) and lay claim to a wide variety of those heme-containing proteins:

hemoglobin, myoglobin, leghemoglobin, non-symbiotic hemoglobin, chlorocruorin, erythrocruorin, neuroglobin, cytoglobin, protoglobin, truncated 2/2 globin, HbN, cyanoglobin, HbO, Glb3, and cytochromes, Hell’s gate globin I, bacterial hemoglobins, ciliate myoglobins, flavohemoglobins

The legal case is likely to keep meat mimetic producers from buying heme derivative proteins for some time. Motif will need deep pockets to see it through and in the meantime Impossible could enjoy a near-monopoly.

Another alternative?

So much for heme for the next while. In Part II we’ll look at a patent from an Australian company which covers another ingredient to help non-meat look and taste like meat.