The potential for a Mars mission in the early 2030s underscores the urgency of developing a road map for advantageous space bio-technologies.The replicative capacity of biology reduces mission launch cost by producing goods on-demand using in situ resources , recycling waste products , and interacting with other biological processes for stable ecosystem function . This trait not only lowers initial launch costs, but also minimizes the quantity and frequency of resupply missions that would otherwise be required due to limited food and pharmaceutical shelf-life on deep space missions. Biological systems also provide robust utility via genetic engineering, which can provide solutions to unforeseen problems and lower inherent risk . For example, organisms can be engineered on-site to produce a pharmaceutical to treat an unexpected medical condition when rapid supply from Earth would be infeasible . A so-called “bio-manufactory” for deep space missions based on in situ resource utilization and composed of integrated biologically-driven subunits capable of producing food, pharmaceuticals, and biomaterials will greatly reduce launch and resupply cost, and is therefore critical to the future of human based space exploration .The standard specifications for Mars exploration from 2009 to 2019 are not biomanufacturing-driven due to the novelty of space bioengineering. Here, we outline biotechnological support to produce food, medicine, and specialized construction materials on a long-term mission with six crew-members and surface operations for ∼ 500 sols flanked by two interplanetary transits of ∼ 210 days . We further assume predeployment cargo that includes in situ resource utilization hardware for Mars-ascent propellant production , which is to be launched from Earth to a mission site. Additional supplies such as habitat assemblies , photovoltaics , experimental equipment, and other non-living consumables will be included. The proposed bio-manufactory would augment processes for air generation and water and waste recycling and purification—typically associated with Environmental Control and Life Support Systems —since its needs overlap but are broader,grow hydroponic and drive a wider development of an array of ISRU, in situ manufacturing , food and pharmaceutical synthesis , and loop closure technologies .
Food, medicine, and gas exchange to sustain humans imposes important ECLSS feasibility constraints . These arise from a crewmember physiological profile, with an upper-bound metabolic rate of ∼ 11–13 MJ/CM-sol that can be satisfied through prepackaged meals and potable water intake of 2.5 kg/CM-sol . Sustaining a CM also entails providing oxygen at 0.8 kg/CM-sol and recycling the 1.04 kg/CM-sol of CO2, 0.11 kg of fecal and urine solid, and 3.6 kg of water waste within a habitat kept at ∼ 294 K and ∼ 70 kPa. Proposed short duration missions lean heavily on chemical processes for life support with consumables sent from Earth . As the length of a mission increases, demands on the quantity and quality of consumables increase dramatically. As missions become more complex with longer surface operations, biotechnology offers methods for consumable production in the form of edible crops and waste recycling through microbial digestion . Advancements in bio-manufacturing for deep space exploration will ensure a transition from short term missions such as those on the ISS that are reliant on single use-single-supply resources to long-term missions that are sustainable.Efficiency gains in a bio-manufactory come in part from the interconnection and modularity of various unit operations . However, different mission stage requirements for assembly, operation, timing, and productivity can lead to different optimal biomanufactory system configurations. A challenge therefore exists for technology choice and process optimization to address the high flexibility, scalability, and infrastructure minimization needs of an integrated biomanufactory. Current frameworks for biomanufacturing optimization do not dwell on these aspects. A series of new innovations in modeling processes and developing performance metrics specific to ECLSS biotechnology is called for, innovations that can suitably capture risk, modularity, autonomy, and recyclability. Concomitant invention in engineering infrastructure will also be required.An estimated ∼ 10,000 kg of food mass is required for a crew of six on a ∼ 900 days mission to Mars . Food production for longer missions reduces this mission overhead and increases food store flexibility, bolsters astronaut mental health, revitalizes air, and recycles wastewater through transpiration and condensation capture . Pharmaceutical life support must address challenges of accelerated instability [ ∼ 75% of solid formulation pharmaceuticals are projected to expire mid-mission at 880 days ], the need for a wide range of pharmaceuticals to mitigate a myriad of low probability medical risks, and the mismatch between the long re-supply times to Mars and often short therapeutic time windows for pharmaceutical treatment.
Pharmaceutical production for longer missions can mitigate the impact of this anticipated instability and accelerate response time to unanticipated medical threats. In early missions, FPS may boost crew morale and supplement labile nutrients . As mission scale increases, FPS may meet important food and pharmaceutical needs . A biomanufactory that focuses on oxygenic photoautotrophs, namely plants, algae and cyanobacteria, enhances simplicity, versatility, and synergy with intersecting life support systems and a Martian atmosphere has been shown to support such biological systems . While plant-based food has been the main staple considered for extended missions , the advent of cultured and 3D printed meat-like products from animal, plant and fungal cells may ultimately provide a scalable and efficient alternative to cropping systems . FPS organisms for Mars use must be optimized for growth and yields of biomass, nutrient, and pharmaceutical accumulation. Providing adequate and appropriate lighting will be a challenge of photo autotrophic-centric FPS on Mars . Developing plants and algae with reduced chloroplast light-harvesting antenna size has the potential to improve whole-organism quantum yield by increasing light penetration deeper into the canopy, which will reduce the fraction of light that is wastefully dissipated as heat and allow higher planting density . Developing FPS organisms for pharmaceutical production is especially complicated, given the breadth of production modalities and pharmaceutical need . Limited resource pharmaceutical purification is also a critically important consideration that has not been rigorously addressed. Promising biologically-derived purification technologies should be considered for processing drugs that require very high purity . Developing FPS growth systems for Mars requires synergistic biotic and abiotic optimization, as indicated by lighting systems and plant microbiomes. For lighting, consider that recent advancements in LED efficiency now make LEDs optimal for crop growth in extraterrestrial systems.The ideal spectra from tunable LEDs will likely be one with a high fraction of red photons for maximum production efficiency, but increasing the fraction of shorter wavelength blue photons could increase crop quality . Similarly, higher photon intensities increase production rates but decrease production efficiency. Understanding the associated volume and power/cooling requirement trade offs will be paramount to increasing overall system efficiency. For microbiomes, consider that ISS open-air plant cultivation results in rapid and widespread colonization by atypicaly low diversity bacterial and fungal microbiomes that often lead to plant disease and decreased plant productivity .
Synthetic microbial communities may provide stability and resilience to the plant microbiome and simultaneously improve the phenotype of host plants via the genes carried by community members. A subset of naturally occurring microbes are well known to promote growth of their plant hosts , accelerate wastewater remediation and nutrient recycling , and shield plant hosts from both abiotic and biotic stresses , including opportunistic pathogens . While SynCom design is challenging, the inclusion of SynComs in life support systems represents a critical risk-mitigation strategy to protect vital food and pharma resources. The application of SynComs to Mars-based agriculture motivates additional discussions in tradeoffs between customized hydroponics versus regolith-based farming,growing lettuce hydroponically both of which will require distinct technology platforms and applied SynComs.Our biomanufactory FPS module has three submodules: crops, pharmaceuticals, and functional foods . The inputs to all three submodules are nearly identical in needing H2O as an electron donor, CO2 as a carbon source, and light as an energy source, with the required nitrogen source being organism-dependent . H2O, CO2, and light are directly available from the Martian environment. Fixed nitrogen comes from the biomanufactory ISRU module. The submodules output O2, biomass, and waste products. However, the crop submodule chiefly outputs edible biomass for bulk food consumption, the pharmaceutical submodule synthesizes medicines, and the functional foods submodule augments the nutritional requirements of the crop submodule with microbially-produced vitamins . These outputs will be consumed directly by crew-members, with waste products entering the LC module for recycling. All submodules will have increased risk, modularity, and recyclability relative to traditional technological approaches. Increased risk is associated with biomass loss due to lowerthan-expected yields, contamination, and possible growth system failure. Increased modularity over shipping known pharmaceuticals to Mars derives from the programmability of biology, and the rapid response time of molecular pharming in crops for as-needed production of biologics. Increased recyclability stems from the lack of packaging required for shipping food and pharmaceuticals from Earth, as well as the ability to recycle plant waste using anaerobic digestion. At a systems integration level, FPS organism care will increase the crew time requirements for setup, maintenance, and harvesting compared to advance food and pharmaceutical shipments. However, overall cost impacts require careful scrutiny: crop growth likely saves on shipping costs, whereas pharmaceutical or functional food production on Mars may increase costs relative to shipping drugs and vitamins from Earth.Maintaining FPS systems requires cultivation vessels/chambers, support structures, plumbing, and tools. Such physical objects represent elements of an inventory that, for short missions, will likely be a combination of predeployment cargo and supplies from the crewed transit vehicle . As mission duration increases, so does the quantity, composition diversity, and construction complexity of these objects. The extent of ISM for initial exploration missions is not currently specified . Nevertheless, recent developments imply that ISM will be critical for the generation of commodities and consumables made of plastics , metals , composite-ceramics , and electronics as mission objects, with uses ranging from functional tools to physical components of the life-supporting habitat . Plastics will make up the majority of high-turnover items with sizes on the order of small parts to bench-top equipment, and will also account for contingencies . Biotechnology—specifically synthetic biology—in combination with additive manufacturing has been proposed an a critical element towards the establishment of off world manufacturing and can produce such polymeric constructs from basic feed stocks in a more compact and integrated way than chemical synthesis, because microbial bioreactors operate much closer to ambient conditions than chemical processes .
The versatility of microbial metabolisms allows direct use of CO2 from Mars’ atmosphere, methane from abiotic Sabatier processes , and/or biologically synthesized C2 compounds such as acetate, as well as waste biomass. A class of bio-plastics that can be directly obtained from microorganisms are polyhydroxyalkanoates . While the dominant natural PHA is poly , microbes can produce various copolymers with an expansive range of physical properties . This is commonly accomplished through co-feeding with fatty acids or hydroxyalkanoates, which get incorporated in the polyester. These co-substrates can be sourced from additional process inputs or generated in situ. For example the PHA poly-lactic acid can be produced by engineered Escherichia coli , albeit to much lower weight percent than is observed in organisms producing PHAs naturally. PHA composition can be modulated in other organisms . The rapid development of synthetic biology tools for non-model organisms opens an opportunity to tune PHA production in high PHB producers and derive a range of high-performance materials. Before downstream processing , the intracellularly accumulating bio-plastics need to be purified. The required degree of purity determines the approach and required secondary resources. Fused filament fabrication 3Dprinting, which works well in microgravity , has been applied for PLA processing and may be extendable to other bio-polyesters. Ideally, additive manufacturing will be integrated in-line with bio-plastics production and filament extrusion.Figure 4 depicts the use of three organism candidates from genera Cupriavidus, Methylocystis, and Halomonas that can meet bio-plastic production. This requires a different set of parameters to optimize their deployment, which strongly affects reactor design and operation. These microbes are capable of using a variety of carbon sources for bio-plastic production, each with a trade-off. For example, leveraging C2 feed stocks as the primary source will allow versatility in the microbe selection, but may be less efficient and autonomous than engineering a single organism like Cupriavidus necator to use CO2 directly from the atmosphere. Alternatively, in the event that CH4 is produced abiotically for ascent propellant , a marginal fraction of total CH4 will be sufficient for producing enough plastic without additional hardware costs associated with ISRU C2 production.