The enabler stack in biomanufacturing 👩🔬
Guest Post in Impact Supporters #2
Intro from August Solliv 👋
Once a month, I invite a friend from the impact VC landscape to write a guest post for Impact Supporters on a specific angle in the impact VC space. These articles are a bit more niche and specific on certain topics. Hope you find it interesting!
This time, I invited Summer to write about the enabler stack in biomanufacturing. Summer and I have spent a lot of time discussing things in the impact space and I am super happy that she wanted to join for a guest post! This article is quite nerdy but also super well-written and in-depth for all of you considering investing in the space. Really hope you enjoy it 💥
If you want to be the next person writing a guest post in Impact Supporters, feel free to text me with your idea and we can discuss the opportunity! E-mail is august.solliv@gmail.com.
Intro about guest post author 👋:
I’m Summer Siman Li, a former investor and management consultant who now drives business operations and strategy at the biomanufacturing startup Enduro. Growing up in Denmark with summers in China gave me an early awareness of inequities and environmental challenges, planting the seeds for a purpose-centric life. I’m excited to scale biomanufacturing alongside the other enablers featured in this post 🙌
Disclaimer: The views expressed are solely my own and this post was completed prior to my employment with Enduro.
An emerging enabler stack for the bio-revolution 🧬
Biomanufacturing has fascinated me since I first encountered innovative biomaterials while sourcing circular packaging solutions for Closed Loop Partners during the 2021 e-commerce boom. Since then, I’ve seen a wave of startups using fermentation, cell culture, and tissue engineering to create new bioproducts and processes.
Yet, outside of niche markets like enzymes, fragrances, and food supplements, biomanufactured products (biosolutions) remain largely inaccessible. This situation is not only bad news for the environment and climate, but also a threat to food security. Biosolutions—which have a far lower carbon footprint and require significantly less water and land than traditional agriculture—are a critical pathway to meeting rising food demand. Hence, curious to understand why biosolutions aren’t yet widespread—and what it would take to see an assortment in my fridge, cupboards, and closet—I began exploring the main challenges and potential solutions through conversations with biomanufacturing startups and VCs. Along the way, I discovered an emerging “enabler” stack: an ecosystem of startups and scale-ups providing critical infrastructure to help biomanufacturing scale effectively.
I’m excited to share the transformative potential of this enabler stack with you.
The main barriers to scaling biomanufacturing 🚧
Biomanufacturing startups face a critical challenge: to compete with traditional products, they must either (1) match the cost and functionality of conventional alternatives (as with drop-in solutions like Again’s acetic acid) or (2) outperform existing products with new, innovative features (as seen in novel bioproducts like K18 Hair’s peptide). To achieve this, startups need to break through three key barriers—capacity, productivity, and cost:
Capacity: Today, bioreactor capacity (the vessels designed to grow microorganisms or cell cultures under controlled conditions for production) and downstream processing capacity are severely lacking, especially at the demo and commercial scale. Only a fraction (15-16%) of current infrastructure is suitable for modern bioprocesses, with most built for outdated chemical or beer production or specialised for pharma applications (Synonym).
Productivity: As production scales up, variables such as temperature become harder to control while mass transfer (e.g., of nutrients) faces limitations, leading to lower productivity (or “titre”, the concentration of a target product) and less efficient processes. This makes it difficult to achieve the productivity required for cost-competitive products.
Cost: The upstream and downstream processes of biomanufacturing remain expensive due to costly inputs, such as feedstocks, and laborious processes (e.g., cleaning).
The relative significance of each hurdle varies across product types. Sufficient capacity, productivity, and costs are much more salient for commodities (like drop-ins for chemicals) than high-value, low-volume products (like enzymes and speciality proteins). Cost-effective production is more crucial for bio-substitutes, which are produced via novel bioprocesses to replace traditional inputs, compared to novel bioproducts, as they offer no additional material value over existing alternatives.
Emerging enablers 🚀
Despite these significant challenges, there is an emerging ecosystem of startups and scale-ups that are working to overcome them, creating what I call an ‘enabler stack.’ These companies address each stage of the biomanufacturing workflow, outlined below, to help unlock the industry's full potential.
Stage 1: Cell/microbe discovery 🔬
Biomanufacturing success relies on a complex, multi-stage workflow. Startups have emerged to tackle each critical phase of this workflow, beginning with the identification of organisms capable of efficient production. Several are working on discovering and developing host microorganisms that can grow effectively in lower-cost conditions and allow for simpler product recovery. For instance, Wild Microbes identifies promising microbes in the wild.
Stage 2: Cell/strain engineering 🥼
Post-discovery, these organisms and their production (metabolic) pathways are optimised. Such optimisation is crucial for enhancing unit economics given the impact on titre which is inversely related to the cost of goods sold (COGS) on a €/kg basis (BCG and Synonym).
Startups tackle this challenge from different angles. Enduro prioritises strain stability—where "strain" refers to a specific variant of a microorganism optimised for production—which tends to deteriorate over fermentation time and when upscaling.
This is achieved by optimising cell-to-cell variation, resulting in higher titre, reduced COGS, and lower bioreactor capacity and CAPEX requirements. Others design enzymes for large-scale conditions and more efficient metabolic pathways, drawing on AI methodologies, e.g., Cradle, and bio-discovery, e.g., Basecamp Research. These enzymes can function under a broader range of conditions, increasing flexibility to optimise operations, reduce production costs, and simplify downstream processing.
Stage 3: Upstream processing 🤝
After optimising the cell or strain, production via cell cultivation or fermentation begins. Upstream processing is well-served with enablers addressing various bottlenecks.
Several contract manufacturing organisations (CMOs) catering to the bioindustrial and food industries have emerged specialising in either cell cultivation (e.g., Extracellular) or fermentation (e.g., Planetary). They make it easier for biomanufacturing companies to test and iterate on a lower budget and upscale.
Novel bioreactors are making it easier to scale production. For example, Swan Neck Bio’s FlexCell single-use bioreactor is designed to reduce costs by eliminating the need for cleaning and sterilisation between batches and decreasing transfers. This technology allows companies to test and scale faster while keeping costs low.
Continuous fermentation is now possible with innovative contamination controls and microbe productivity extension, allowing fermentations to run for weeks and months, reducing downtime and cleaning costs vis-a-vis traditional batch processes. This unlocks productivity increases (around 5x at Cauldron), lowers COGS, and significantly decreases bioreactor capacity and CAPEX requirements.
Alternative feedstocks from upcycled waste streams such as agricultural waste, gases from industrial processes, and cellulosic materials are available, enabling cost savings while reducing land use and CO2 emissions. Hyfé addresses the challenge of high input costs by transforming wastewater components from food manufacturing facilities into feedstock for biomanufacturing companies, creating cost savings and circularity.
Stage 4: Downstream processing ⚗️
Lastly, the product is isolated, purified, processed, and packaged. This stage remains underserved. While startups like DAB offer integrated solutions that cover both upstream and downstream processing—where fermentation improvements simplify product recovery—significant optimisation opportunities remain across various processes and technologies in downstream processing.
Transversal enablers 🤓
Beyond the individual stages of biomanufacturing, a set of transversal technologies exists. These tools are critical across the entire value chain and support innovation across multiple stages.
Cell-free technology utilises immobilised enzymes extracted from cells to catalyse specific biochemical reactions rather than hosting the reactions in living cells. Though less mature, cell-free systems hold the potential to lower production costs by eliminating the need for organisms and enabling the use of standard chemical reactors, as demonstrated by Enginzyme, instead of scarce bioreactors.
Lab automation platforms accelerate the R&D work during the early stages from optimising protocol design (Aradon) to connecting to lab instruments to automate these protocols (Monomer).
End-to-end bioprocess solutions that are plug-and-produce have also emerged within cell cultivation. Cellcraft and Innocent Meat both offer complete production solutions, including all biological ingredients and bioreactors, for easy set-up of cultivated meat production.
Bioinformatics solutions specifically developed for biomanufacturing increase efficiency and generate cost savings throughout the workflow. The solutions contribute in various ways, such as improving data management and insights at Invert and reducing the need for traditional lab experiments through virtual cell simulations at Fungtional Bio.
Source: Summer Siman Li’s own creation
The biomanufacturing enablers (excluding those focused solely on biopharma) mapped above 👆 form a global ecosystem, though strongly clustered in Europe and the U.S. These startups and scale-ups range from those reliant on soft funding to pre-Series E, with the majority in seed and Series A stages. Their core competencies, business models, and primary customers vary—some focus on supporting biomanufacturing startups, while others cater more to established bioindustrial giants. Yet together, they provide infrastructure and services that bring us much closer to a bio-revolution.
Concluding thoughts: Investing in the future of biomanufacturing 💼
The past few years have undoubtedly been challenging for biomanufacturing—marked by reduced investment, startups winding down, and significant consolidation. Yet, the companies that have weathered this storm have emerged more resilient and strategically positioned for growth. As Max Mundt aptly described, we are approaching a “phoenix rising from the ashes” moment.
For impact investors, this is a moment of opportunity. For those seeking to catalyse sustainable change and foster market-shaping technologies, here are my recommendations:
Focus on high-impact stages: Biomanufacturing’s enabler stack is vast, yet specific stages—particularly downstream processing—have unmet needs and high-impact potential. Investing in these underdeveloped areas can drive much-needed advancement.
Prioritise versatility and adaptability: The diversity of processes across biomanufacturing underscores the need for versatile or easily customisable solutions.
Leverage synergies: Biomanufacturing thrives on collaboration, where tools and innovations enhance each other’s impact. Look for investments with cross-functional potential, and champion partnerships that build a stronger, interconnected ecosystem.
Seek dual-impact opportunities: Investors focused on both planetary and human health can find “two-for-one” opportunities in startups advancing both bioindustrial and biopharma production.
Integrate enablers: When considering investments in bioproduct companies—those making novel bioproducts or bio-substitutes—evaluate how they have or can incorporate enabler technologies to reduce costs and accelerate time to market. Factor enabler integration into your due diligence.
By fostering this ecosystem of enablers today, impact investors have a unique chance to fuel a bio-revolution that could redefine sustainable production and course-correct our climate trajectory.
Acknowledgements 🙌
I would like to thank Max Mundt at Amino Collective, the other participants in the biomanufacturing ripple at The Drop, and Mark Emil Hermansen at Swan Neck Bio for their invaluable insights and support.
Thanks for reading this guest post! Hope you found it interesting and that you like these more in-depth articles with super knowledgable guests.
See you soon for the next weekly issue, and next month for the next guest post! 👋