A crewed mission to and from Mars may include an exciting array of enabling biotechnologies that leverage inherent mass, power, and volume advantages over traditional abiotic approaches. In this perspective, we articulate the scientific and engineering goals and constraints, along with example systems, that guide the design of a surface biomanufactory. Extending past arguments for exploiting stand-alone elements of biology, we argue for an integrated biomanufacturing plant replete with modules for microbial in situ resource utilization, production, and recycling of food, pharmaceuticals, and biomaterials required for sustaining future intrepid astronauts. We also discuss aspirational technology trends in each of these target areas in the context of human and robotic exploration missions.

Space bioprocess engineering (SBE) is an emerging multi-disciplinary field to design, realize, and manage biologically-driven technologies specifically with the goal of supporting life on long term space missions. SBE considers synthetic biology and bioprocess engineering under the extreme constraints of the conditions of space. A coherent strategy for the long term development of this field is lacking. In this Perspective, we describe the need for an expanded mandate to explore biotechnological needs of the future missions. We then identify several key parameters—metrics, deployment, and training—which together form a pathway towards the successful development and implementation of SBE technologies of the future.

A mechanistic understanding of host-microbe interactions in the gut microbiome is hindered by poorly annotated bacterial genomes. While functional genomics can generate large gene-to-phenotype datasets to accelerate gene discovery, their applications to study gut anaerobes have been limited. For instance, most gain-of-function screens of gut bacterial genes have been performed in an aerobic host and included a small number of conditions. To address these challenges, we developed a strategy to barcode expression libraries for high-throughput interrogation of gene functions in competitive fitness assays. We demonstrate the power of this approach to uncover novel phenotypes for uncharacterized genes using pooled libraries constructed from a diverse set of gut Bacteroidales expressed in Bacteroides thetaiotaomicron. We identified new roles in carbohydrate metabolism for nine proteins, including enzymes, transporters, a regulator, and hypothetical proteins from mobile genetic elements. This approach can be readily applied to other organisms and additional phenotypic assays.

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 mission resilience, flexibility, and efficiency by virtue of its ability to efficiently utilize in situ resources and reclaim resources from waste streams. Since its infancy during the Apollo years, biotechnology, and specifically biomanufacturing, have witnessed significant expansions of scope and scale. Here we outline four primary mission classes, on Luna 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. We see that as mission duration and distance from Earth increase, the benefits of specialized sustainable biomanufacturing processes increases. Here we present a strategic approach, guided by technoeconomics, to development, testing, and deployment of these technologies serves to nucleate the larger effort of supporting a sustained human presence in space. The processes needed for each scenario spans the technical breadth of synthetic biology to design engineering, from sophisticated genetic tailoring of chassis-organisms to building scalable, automated, easily operable bioreactors and processing systems. As space-related technology development often does, these advancements are likely to have profound implications for the creation of a stable, resilient bioeconomy on Earth.

NASA mission systems proposals are often compared using an equivalent system mass (ESM) framework, wherein all elements of a technology to deliver an effect—its components, operations, and logistics of delivery—are converted to effective masses, which has a known cost scale in space operations. To date, ESM methods and the tools for system comparison largely fail to consider complexities stemming from multiple transit and operations stages, such as would be required to support a crewed mission to Mars, and thus do not account for different mass equivalency factors during each period and the inter-dependencies of the costs across the mission segments. Further, ESM does not account well for the differential reliabilities of the underlying technologies. The uncertainty in the performance of technology should incur an equivalent mass penalty for technology options that might otherwise provide a mass advantage. Here we draw attention to the importance of addressing these limitations and formulate the basis of an extension of ESM that allows for a direct method for analyzing, optimizing, and comparing different mission systems. We outline a preliminary example of applying extended ESM (xESM) through a techno-economic calculation of crop-production technologies as an illustrative case for developing offworld biomanufacturing systems.

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 techno-economics 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.