The gut microbiome is essential to maintain overall health and prevent disease, which can occur when these microbes are not in homeostasis. Microbial biotherapeutics are important to combat these issues, but they must be alive at the time of delivery for efficacy. Many potentially therapeutic species are anaerobes and thus are difficult to manufacture because of the limited efficacy of existing protective methods, making their production nearly impossible. We have developed a self-assembling cellular coating to improve the viability and stability of the next-generation biotherapeutic Bacteroides thetaiotaomicron. We show protection from both harsh processing conditions and oxygen exposure, even in the absence of canonical cryoprotectants. This advance will increase the range of microbes that can be stably manufactured and facilitate the development of emerging strains of interest by ensuring their postproduction viability.

Significance: Metabolic engineering benefits from the tunable and tightly controlled transformations afforded by biological systems. However, these reactions have generally been limited to naturally occurring pathways and products. In this work, we coopt metabolic electron transfer fromShewanella oneidensisto control the activity of an exogenous metal catalyst in an abiotic reaction scheme: atom-transfer radical polymerization. In the presence ofS. oneidensis, polymerizations exhibited well-defined kinetics and yielded polymers with controlled molecular weights and low polydispersities. Additionally, polymerization activity was dependent on electroactive metabolism and specific electron transport proteins, both of which provide handles to control material synthesis. This work serves as a proof-of-principle toward expanding the scope of reactions available to metabolic engineers to include previously discovered transition-metal–catalyzed reactions.