Developing a Commercial-Ready Production Microbe and Process - The 1,4-Butanediol Story

Genomatica has established an integrated computational and experimental technology platform¹ to design, build, and optimize high-producing microorganisms and fermentation-based processes for the production of a broad variety of chemicals from renewable feedstocks^{2, 3}. The platform enables the development of cost-effective, sustainable processes that will compete with and ultimately displace existing processes that rely on fossil fuel raw materials. Our first product, 1,4-butanediol (BDO)⁴, is a 1.8 billion kg/year industrial chemical used in numerous applications including polymers such as spandex (PTMEG), poly(butyleneterephthalate) (PBT), and polyurethanes. This presentation will highlight the process-first approach that led to a final production microbe that produces BDO at a high titer, rate, and yield with minimal soluble byproducts to simplify and improve the economics of downstream recovery. Key recent advances include increasing ATP and NADPH availability, identifying the rate-limiting pathway enzyme, improving its activity and substrate specificity, rebalancing sugar uptake with increased pathway capacity, eliminating sources of genome instability, and developing a robust scalable fermentation process that accentuates the strengths of the final production microbe. To our knowledge, this is the first example of a successfully developed commercial-scale process (validated at scale within 6 years of project initiation) for a bio-based â??exact sameâ? commodity chemical that will compete directly with existing petro-based processes⁵.

¹ Barton, et al., 2015, J Ind Microbiol Biotechnol, 42(3), 349-60
² Burk, 2010, Int Sugar J, 112(1333)
³ Van Dien, 2013, Curr Opin Biotechnol, 24(6), 1061-1068
⁴ Yim, et al., 2011, Nat Chem Biol, 7(7), 445-52
⁵ Burgard, et al., 2016, Curr Opin Biotechnol, 42, 118-125