The Future of Biomanufacturing: Bridging the Gap Between Upstream and Downstream Processes

Significant strides have been made in optimizing microbial strains and enhancing efficiency in biomanufacturing. However, a persistent disconnect between upstream and downstream operations continues to hinder overall progress. This assertion comes from Dr. Michael Tai, cofounder of Boston Bioprocess.

Formation and Focus of Boston Bioprocess

Established in Boston in 2022 by Dr. Tai, who previously led bioprocessing efforts at Motif FoodWorks, and Ted Netland, Boston Bioprocess relocated to Champaign, Illinois, in 2023. The firm specializes in offering fermentation and downstream processing services at both benchtop and pilot scales, catering to a diverse clientele that ranges from startups to established companies seeking to refine their processes or innovate new products.

Insights from the Field

During a recent conversation with AgFunderNews (AFN) at the SynBioBeta conference in San Jose, Dr. Tai shared his insights on the current barriers facing the bioeconomy.

Addressing Existing Challenges

AFN: What original problems motivated the founding of Boston Bioprocess?

Dr. Tai: Upon founding Boston Bioprocess, we recognized a notable gap in the offerings related to bench development and process scaling compared to the robust capabilities present in strain engineering. While proficiency in a 500-liter bioreactor is common, accurately predicting performance in a 500,000-liter bioreactor remains elusive.

Additionally, integrating upstream fermentation performance with downstream processes poses challenges. For instance, if we increase anti-foam additives during fermentation, we still struggle to predict the effects on downstream yield.

Integration of Processes

It’s crucial to enhance integration between upstream and downstream workflows. Despite investments aimed at optimizing fermentation, downstream process resources remain limited. This imbalance could lead to downstream yield sacrifices.

Exploring Microbial Potential

AFN: Do we need a broader range of microbial workhorses for industrial bioprocessing?

Dr. Tai: We have two options. One is to further engineer established industrial microbial hosts, such as Pichia, enhancing our understanding and capabilities. Alternatively, we can allocate more resources toward exploring wild microbes that possess unique characteristics.

Both approaches have their advantages and drawbacks. While established chassis can facilitate targeted protein expression, they may also face productivity issues when too many plasmids are introduced. On the other hand, domestication of wild-type microbes like Trichoderma presents its own challenges but could yield significant protein production.

The Promise of Continuous Fermentation

AFN: Could continuous fermentation revolutionize product development?

Dr. Tai: There are compelling application scenarios, especially with biomass fermentation focusing on quantity and nutritional value. However, when specific functionalities are necessary, challenges arise. Maintaining high productivity over extended fermentation periods can be difficult, particularly when switching from growth to product expression phases.

Conclusion and Future Direction

To move forward, the biomanufacturing sector must prioritize the integration of upstream and downstream processes and explore new microbial avenues. Bridging these gaps is essential for building a more resilient biotechnology industry.

Further Reading

• From jumping genes to designer genomes: Anthology’s blueprint for smarter bioproduction strains
• Enduro Genetics aims to deliver its first two projects this year to turbocharge bioproduction: ‘We’re taking some of the ‘bio’ out of biomanufacturing’
• Biosphere emerges from stealth, raises $8.8m for UV-sterilized bioreactors it claims can slash bioproduction costs