Microbial biomanufacturing for space-exploration—what to take and when to make

Perspective https://doi.org/10.1038/s41467-023-37910-1 Microbial biomanufacturing for spaceexploration—what to take and when to make Received: 18 July 2022 Accepted: 5 April 2023 Nils J. H. Averesch 1,2,12 , Aaron J. Berliner 1,3,12 , Shannon N. Nangle4,5,12 Spencer Zezulka 1,3,6, Gretchen L. Vengerova 1,3, Davian Ho1,3, Cameran A. Casale1,3, Benjamin A. E. Lehner7, Jessica E. Snyder8, Kevin B. Clark9,10, Lewis R. Dartnell11, Craig S. Criddle1,2 & Adam P. Arkin 1,3 , As renewed interest in human space-exploration intensifies, a coherent and modernized strategy for mission design and planning has become increasingly crucial. Biotechnology has emerged as a promising approach to increase resilience, flexibility, and efficiency of missions, by virtue of its ability to effectively utilize in situ resources and reclaim resources from waste streams. Here we outline four primary mission-classes on Moon and Mars that drive a staged and accretive biomanufacturing strategy. Each class requires a unique approach to integrate biomanufacturing into the existing mission-architecture and so faces unique challenges in technology development. These challenges stem directly from the resources available in a given mission-class—the degree to which feedstocks are derived from cargo and in situ resources—and the degree to which loop-closure is necessary. As mission duration and distance from Earth increase, the benefits of specialized, sustainable biomanufacturing processes also increase. Consequentially, we define specific design-scenarios and quantify the usefulness of in-space biomanufacturing, to guide technoeconomics of space-missions. Especially materials emerged as a potentially pivotal target for biomanufacturing with large impact on up-mass cost. Subsequently, we outline the processes needed for development, testing, and deployment of requisite technologies. As space-related technology development often does, these advancements are likely to have profound implications for the creation of a resilient circular bioeconomy on Earth. 1234567890():,; 1234567890():,; Check for updates With reinvigorated curiosity and enthusiasm for space-exploration and increasingly complex campaigns, humanity prepares to return to the Moon en route to Mars1–3. Efforts to modernize mission architectures4,5—combinations of inter-linked system elements that synergize to realize mission goals6—will need to leverage an array of enabling technologies including biomanufacturing towards the realization of such grand visions7–9. Microbial biomanufacturing has the potential to provide integrated solutions for remote or austere 1 Center for the Utilization of Biological Engineering in Space (CUBES), Berkeley, CA, USA. 2Department of Civil and Environmental Engineering, Stanford University, Stanford, CA, USA. 3Department of Bioengineering, University of California Berkeley, Berkeley, CA, USA. 4Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. 5Circe Bioscience Inc., Somerville, MA, USA. 6School of Information, University of California Berkeley, Berkeley, CA, USA. 7Department of Bionanoscience, Delft University of Technology, Delft, South Holland, Netherlands. 8Blue Marble Space Institute of Science, Seattle, WA, USA. 9Cures Within Reach, Chicago, IL, USA. 10Champions Program, eXtreme Science and Engineering Discovery Environment (XSEDE), Urbana, IL, USA. 11Department of Life Sciences, University of Westminster, London, UK. 12These authors contributed equally: Nils J.H. Averesch, Aaron J. e-mail: ; ; Berliner, Shannon N. Nangle. Nature Communications | (2023)14:2311 1 Perspective https://doi.org/10.1038/s41467-023-37910-1 locations, especially where supply chains for consumable and durable goods cannot operate reliably10,11. Complementary to, but distinguished from merely remediative and extractive microbial functions, such as biomining12,13, off-world biomanufacturing corresponds to any deployable system that leverages biology as the primary driver in generating mission-critical inventory items of increased complexity, i.e., the de novo synthesis of components for the formulation of food, pharmaceuticals, and materials8,10,14,15. When integrated effectively into mission architectures, bio-based processes could significantly de-risk crewed operations through increased autonomy, sustainability, and resilience, freeing up payload capacity16. Key to the efficacy of biotechnology as a support of human space-exploration is its efficiency in using locally available resources (in situ resource utilization, ISRU) and the ability to utilize waste streams from other mission elements and recycle its own products (loop-closure, LC)17–19. As missions expand, progressive advancement and wider implementation of in situ (bio)manufacturing (ISM/ bio-ISM) will lead to greater independence, enabling more complex mission-designs with extended goals, and may eventually allow a self-sufficient human presence across the solar system to be sustained. Biomanufacturing is appropriate for that purpose, because high-volume resources, like fixed carbon and nitrogen (as well as low-volume, but critical resources such as minerals) can be produced and recovered in compact autonomous systems that are analogous to Earth’s biogeochemical cycles20–24. Biochemistry also provides access to a plethora of organic compounds, often at unrivaled purity and selectivity, many of which are not accessible by other means25,26. Biologically-driven ISM in support of space-exploration becomes more significant the deeper humans venture into space: As the support of supply chains becomes increasingly challenging the further humans travel, ISM is most feasible in locations where resources are available, accessible and abundant, such as the Moon27, but even more so Mars (Fig. 1b). The advantages and drawbacks of biotic and abiotic approaches for ISM, in particular for life-support but also auxiliary functions for extended human operations beyond Earth-orbit have previously been discussed at length8,10,28,29 (also see Table 1 in the Supplmentary Information), but an actionable roadmap for deploying biomanufacturing-based systems within upcoming campaigns has yet to be formulated. Here, we discuss the applicability of biologically driven ISRU and LC in the context of different off-world mission classes, and conduct a qualitative techno-economic analysis (TEA) to unravel the inventories of different mission-design scenarios of spacetravel. Following the TEA, we lay out paths for readying bio-based technologies for deployment and inclusion into mission-architecture, to enable the next phase of roadmapping for crewed missions into deep-space. Fig. 1 | Approaches to in situ biomanufacturing (bio-ISM) depending on offworld mission-class. The context-specific off-world mission-classes 1 to 4 are defined in (a), mapped as quadrants on qualitative spectra for the availability of in situ resources and logistic resupply. The most ub (...truncated)