Precision fermentation’s capacity craze: Have we lost the plot?

Using microbial organisms like yeast and fungi as cell factories to produce animal proteins, Pat Brown and his early team at Impossible Foods kicked off the modern precision fermentation industry.

Within a few years, Clara Foods, Geltor and Perfect Day were using the technique to produce a variety of egg, dairy and collagen ingredients. By the late 2010s, these first movers raised hundreds of millions of dollars and dozens of other startups followed in their footsteps.

Overreliance on the capacity narrative

Today, recognition of the industry’s promise is mainstreaming. Environmental figures like George Monbiot are declaring that precision fermentation “may be the most important green technology ever.” Supporters are positioning it as a promising solution to the constrained supply of conventional animal products.

Given the fervor, investors, as well as the commentariat, are prodding companies to begin large-scale production ASAP. So, the industry’s conversational spotlight has now fixed on: How do we build enough capacity to meet future demand, which could soar into the tens of millions of tonnes by 2030? A tantalizing and no doubt important question.

However, this almost singular focus on capacity is troubling. It seems to imply: The unit economics of precision fermentation are essentially solved and all that remains is to build factories. We will eventually need lots more factories, yes.

The precision fermentation sector should not be bashful about its pursuit of an all-out biomanufacturing industrialization, a necessary condition to outcompete animal agriculture. But we must also stay honest to the science, which says the crucial work to be done in precision fermentation for cheap animal-free alternatives is not simply building or enabling capacity but rather designing new or radically improved production systems.

I’ll let you in on an open secret: Leading scientists and technologists from the industry and academia tend to tell me — often in hushed tones and sometimes only off the record — that the economics of food-grade precision fermentation is nowhere near competing with commodity dairy or eggs.

This problem, they warn, will not be solved by simply upscaling to larger tank volumes. At best, scaling up production to immense tank volumes will reduce costs by 35% to 40% instead of the many-fold reduction needed.

Precision fermentation is more like cultivated meat than we think

Some industry insiders today believe the difficulty of the technologic challenge — designing cost effective bioprocesses that produce cheap recombinant food proteins in millions-of-ton quantities — bears close resemblance to that of scaling cultivated meat production. It would be unwise to suggest the cultivated meat industry should place an immediate effort to build large-scale production facilities at the very top of its priority list.

The key message from David Humbird’s seminal cultivated meat techno-economic assessment was not that it will be impossible to drive the cost of cultivated meat to an acceptable level. Rather, it will be impractical to do so without moving away from pharmaceutical-style animal cell bioprocessing, which has effectively been the cultivated meat industry’s base case scenario from the very beginning.

The bioprocesses that will enable truly low-cost, competitive cultivated meat production only exist within the small army of research labs, startups, and consortia dedicated to designing entirely new cultivated meat bioprocesses. In precision fermentation, as in cultivated meat, the priority should be designing and validating these new processes rather than scaling legacy systems.

Getting creative

To get the economics of precision fermentation right for large-volume commodity food products, the industry would do well to focus on a few areas where radical rather than incremental process intensification is possible:

• Take the Ginkgo approach. To precision fermentation cognoscenti, this tactic is the most obvious. That is, wage all-out warfare on host organism physiology. Engineering higher protein expression levels, or titers, is still rightly viewed as among the highest marginal return activities. Although, some experts believe we are beginning to reach plateaus in terms of max titers of common workhorse strains like P. pastoris and T. reesei.
• Enhance the space-time yield. Continuous processing or perfusion culture is a longstanding goal in bioprocessing across many disciplines. The potential for fully automated, around the clock production means we can produce substantially more product, in a shorter time period, in smaller production settings.
• Rethink bioseparations. Downstream processing, the deceivingly complex process of separating the protein of interest from the rest of the fermentation broth, can account for over half of production costs in low purity, industrial enzyme production and up to 85% of costs in the manufacture of pharmaceutical biologics. Yet there are few to no downstream unit operations specifically designed for this industry.
• Learn from oil and gas. Refineries in the petrochemical industry can be exceptionally good at valorizing co-product streams. The PF industry should adopt a biorefinery mindset, wherein it proactively develops valorization strategies for high-volume waste streams. Microbial biomass, for instance, will be produced in colossal quantities as the sector industrializes.

There are applications of precision fermentation — chymosin, niche cosmetic proteins and next-generation sweeteners — that today are economically competitive in the market because they are less structurally complex, have relaxed sterility requirements, command high prices or are used in small quantities.

These applications are ready for large-scale manufacturing. Perhaps especially so if facilities are designed with modular skids that can incorporate new bioprocesses over time.

But let’s not lose sight that for mainstream products facing intense pricing pressures — dairy and egg proteins among others — and are at the heart of the industry’s grandest ambitions, the industry should be investing primarily in creative solutions for process intensification. This alone will unlock price parity in these categories. Let’s avoid building bridges to nowhere.