Optimising plant form and function for controlled environment agriculture in space and on earth

Planned missions to Mars and the moon stress the urgency of developing self‐sustaining food production systems for crewed, long‐term, space exploration. Here we discuss space agriculture (SpaceAg) as a sustainable complete life support system for prolonged space travel and surface missions. The unique challenges and considerations for cultivating crops in space, where radiation, gravity, atmosphere and temperature differ from Earth, are presented. We discuss the selection of suitable crops and approaches to optimise growth traits for the ideal plant form, including the potential of genetic engineering to enhance yield and nutritional content. Plants can serve multiple roles, from providing nutritious foods and wellbeing to acting as biofactories for essential pharmaceuticals. The need for robust and efficient controlled environment agriculture (CEA) systems that are integral to life support is explored. Finally, we discuss promising solutions for sustainable agriculture in controlled environments on Earth, based on SpaceAg research and innovation.


INTRODUCTION
As the frontiers of human exploration expand beyond Earth's atmosphere, the pursuit of sustainable life in outer space has become a focus of scientific and technological innovation.The ambition to establish permanent human settlements on Mars and the moon has transformed from a distant dream into a tangible goal due to the increasing efforts of both national space agencies and several commercial entities. 1The US National Aeronautics and Space Administration's (NASA) Artemis initiative aims to construct an orbiting lunar space station (Gateway) to facilitate landing people on the lunar surface by 2024. 2 The corporation SpaceX aims to establish a settlement on Mars with one million inhabitants by the year 2050. 3There are numerous technical challenges that must be addressed for extended missions to space to succeed.Not least, sufficient food must be provided for astronauts.Food crops will need to be grown in space because carrying the complete food supply for a mission as a payload is not feasible; it requires too much mass, and many food products may spoil in the long duration flight. 4,5rews on space missions currently rely on prepackaged foods, which provide a monotonous and relatively unappealing diet.The result is that crew members frequently do not consume sufficient calories, which results in health and performance impacts. 6rowing plants on space missions would offer new food options, as the crew members gain access to fresh, nutritious produce. 7The current reliance on prepackaged diets could be replaced or enhanced with a diverse array of crops grown in space, fostering variety and interest in their daily meals.By customising their diet with freshly harvested produce, the diets of crew members could be optimised for nutritional intake and wellbeing, thus enhancing their physical resilience during the arduous challenges of space travel (Figure 1).
Growing plants in space can also provide benefits beyond food, such as maintaining air quality.The closed environment of a spacecraft demands effective air purification systems.Through photosynthesis, plants efficiently remove carbon dioxide and release oxygen, thereby fostering life-supporting atmosphere (Figure 1).Furthermore, the inclusion of greenery within the confined space station supports the psychological well-being of the crew members. 8The mere presence of living plants can provide a soothing ambience, alleviate stress, and heighten the crew's overall enjoyment of their space journey.Notably, the sensory experiences of sight, smell, and taste derived from the cultivation of familiar Earth vegetation in space can offer a comforting connection to their home planet, promoting mental health and emotional stability (Figure 1). 8f we wish to harness the many benefits of growing plants in space, then we must develop innovations in plant design and create automated, highly efficient growth facilities that promote sustainability. 9These state-of-the-art systems should prioritise low-input and low-waste paradigms, ensuring that plants can thrive with minimal resources and waste products can be efficiently recycled.Controlled Environment Agriculture (CEA) can address these challenges and produce food such as fresh herbs, vegetables, and fruits, with lower nutrient, water and space use than conventional agriculture. 10dvances in plant cultivation and plant-derived products for space will also have important applications on Earth.Space habitation and settlement will be extremely resource-limited, particularly in terms of power and water.Solutions developed for space will consequently provide new technologies to drive sustainability on-Earth.These might include plant cultivars with improved yield and performance in CEA, and a better understanding of how to operate CEA facilities at high resource efficiency.
In this review, we propose several areas of research and development to produce plants suited to space settlements, particularly Mars and the Moon, as these are current targets for crewed missions.We consider issues around food and nutrition, and other potential applications of plants such as the production of medicines and materials.We highlight technologies and pathways through which these plants might be generated and lastly, discuss the on-Earth applications of space plants.

THE CHALLENGES OF GROWING PLANTS IN SPACE
Plants grown in space will face exceptionally challenging conditions, even in established settlements.Although plants need very few inputs to grow light, water, CO 2 and basic nutrients, there are further requirements if they are to thrive, and environmental boundaries to their existence.For example, on Earth, plants are adapted to day length regimes and light intensities depending on their F I G U R E 1 Benefits of growing plants in space.These include the production of fresh, nutritionally optimised food; using plants as biofactories to produce medicine and vaccines; air and water purification; and mental health benefits.
MODERN AGRICULTURE geographical location, are vulnerable to extreme temperatures, and have had one constant during all evolution-gravity.Gravity will be altered in space settlements, with martian gravity at 38% and lunar gravity at 16% of that on Earth.Plants have shown remarkable plasticity to reduced gravity during a growing cycle, but the long-term effects on reproduction and seed germination over generations are unclear.Altered seed composition has been shown to occur in plants grown in space and will influence both nutritional quality and delay growth. 11Plant roots are particularly sensitive to low gravity and this may impact strategies they have developed to explore the soil for water and nutrients, and potentially their interactions with the soil microbiome. 12,13As a consequence, agricultural systems in space will require protection from radiation and extreme temperatures, controlled gas levels, optimised lighting for plant growth and energy conservation, and recycling of water and nutrients.This means that all plants will be grown in advanced CEA facilities.

Temperature, light and radiation
The lack of atmosphere around the moon and Mars creates three interlinked challenges: temperature control, light availability and radiation exposure.The ability to trap the sun's energy is limited by the absence of atmosphere, so temperatures on the moon can range from 121°C in daylight to −133°C at night near the equator.Similarly, radiation exposure at the surface is elevated without atmosphere principally due to galactic cosmic radiation and solar energetic particles. 14,15lants and humans will need protection from these extremes when settlements are established on the moon, Mars, and elsewhere.Growth habitats will consequently either have to be underground or heavily insulated, meaning that lighting for plants will be filtered or generated from LEDs.Plants have complex pathways involved in perception and response to different types of light (dawn/dusk, cloud, shade), which in turn regulate many developmental pathways including seedling growth, shoot and root biomass and architecture, flowering time, and signalling related to hormones and stress. 16Plants also vary considerably in response to light intensity, with some plants able to maintain photosynthesis in high light intensities, whilst in others these results in inhibition and damage to light capturing systems. 17Light regimes in space experiments have largely been at consistent intensity and wavelengths with strict 'on/off' durations of dark and light.A challenge will be exploring the optimal light levels and wavelengths, including UV, blue and red/farred light, at given times of day and stages of plant development, keeping in mind that different plant species will have distinct responses.Light can additionally regulate nutritional composition including the amount and type of bioactives, and avenues exist to use light as a regulatory switch to produce specific compounds on demand. 18emperature will either need to be controlled to stay within plant production limits or plant traits adapted to tolerate more extreme conditions.China's landing of the Lunar Micro Ecosystem on the far-side of the moon in 2019 carried potato, canola, cotton and Arabidopsis seeds. 19Cotton seeds survived the extreme temperature to germinate, but after only a few days succumbed to the bitter cold.At the poles, where habitation is likely due to water deposits, temperatures can be even more extreme.To date, growth chambers used in space have either relied on temperature regulation as part of the cabin atmosphere or had independent temperature control to the surroundings. 20However, the maintenance of a comfortable cabin temperature is likely too simplistic.Plants have complex mechanisms that sense and adapt to changes in temperature on Earth associated with day/night cycles and seasons, and this information frequently acts as a developmental cue.For example, tulip bulbs require a period of cold before germinating and in many plant, temperature is one of the signals involved in flowering. 21Exploring the potential of temperature to improve growth in space is an area requiring further investigation.

Constraints on energy and physical space
CEA systems for plant growth in space must have a limited footprint, making efficient use of all the threedimensional space because all cultivation areas must be under atmosphere and climate control, which is very costly.The challenge of requiring a small footprint can be approached by using vertical farming systems, which are a form of CEA that has gained recognition for high efficiency crop production.Vertical farming systems attempt to maximise space by stacking horizontal shelves in layers.They have undergone significant technical development in recent times and have the capacity to reliably provide high yields per unit of area compared to traditional agriculture, yet this comes with significant energy requirements.Sunlight is a powerful 'free' energy source for plants.Vertical farming, and CEA more broadly, uses large amounts of energy to supply artificial lighting and to control the climate (temperature, humidity) within the enclosed system. 22he heat emission by the lighting system compounds climate control issues.LEDs have dramatically increased efficiency, but further advances are needed to improve system economics.Strategies will need to be developed to reduce the energy used for lighting whilst maintaining optimal photosynthetic capacity, yield and nutritional content.These could include providing low or intermittent lighting or technologies such as photo-selective films which filter out certain wavelengths without loss of light intensity. 23,24mproving the amount of edible plant material and the speed of plant growth would also improve productivity per unit area, effectively reducing energy consumption per unit of yield.These might be achieved by reducing root biomass and plant stature, employing fastflowering varieties, and using fast growing plants such as duckweed (discussed further in 'Ideal plant form for space' section).

Water, nutrient and growth substrate limitations
Soil is the normal substrate for plant cultivation on Earth, providing essential nutrients, porosity for water, and mechanical support, but sufficient quantities cannot be transported to space.Alternative growth mediums will have to be used for plants in space, which must address the challenges of water and nutrient distribution in low gravity and pressure environments.Gravity on Earth helps drain water, enabling movement and gas exchange around the root and water recovery.In microgravity, as experienced on the International Space Station (ISS) and during spaceflight, water can surround roots and cause a lack of oxygen, known as anoxia or hypoxia. 25Issues could arise with flooding or drying out as growth systems attempt to balance water and oxygen supply. 26The severity of these issues in the low (but not micro-) gravity of Mars and the moon is not yet known due to a lack of experimental data.Growing the model plant Arabidopsis on lunar regolith showed that although plants could germinate, growth was slow and plants were severely stressed. 27For this reason, any growth medium used is likely to be transported from Earth initially, so will have to be of minimal size and mass.Systems that explore 'soil-less' mediums such as hydro-or aeroponics have huge potential yet need to overcome the challenge of 'goldilocks' nutrient delivery at the root interface.On the ISS Veggie system, designed for small-scale plant cultivation, controlled-release fertilizers incorporated into the substrate 'arcillite', a calcinated montmorillonite and illite clay, and wicking with water was found to be the most reliable means of nutrient transfer to roots. 28arious designs of porous or perforated tubing have been tested and 'active' systems that have sensors to monitor and adapt nutrient and water delivery to avoid stress will need to be developed and tested for future large-scale production. 20Systems such as the EU Horizon 2020 TIME SCALE project are testing restricted root volumes, the influence of transpiration rates and water uptake related to nitrate and salts to provide essential information for future missions. 29The supply of fertilizers using non-edible plant mass and human waste are further areas for exploration.The sustainability of hydroponic/aeroponic systems will be advantageous in space, given that they may use 90%-99% less water than open agriculture. 22They also provide the ability to collect and recirculate water and nutrients, which will be essential in SpaceAg.
Attempts have been made to grow crops in simulated space environments and to incorporate bioregeneration of water and/or waste matter.The EDEN ISS greenhouse in Antarctica achieved a yearly production capacity of 27.4 kg/m2 of edible biomass from lettuce, leafy greens and fresh vegetables. 30China's 105-day Lunar Palace 1 mission aimed to support 55% of the food requirements for three crew members. 31In NASA's current Mars CHAPEA (crew health and performance exploration analog) 1-year missions, four crew members will grow fresh fruit and vegetables in a crop growth system for 1 year.These and other simulation experiments have illustrated that meeting 100% of human nutritional needs sustainably and with a limited footprint is challenging enough on Earth.Space will significantly increase the difficulty.

CURRENT AND FUTURE SPACE CROPS
A balanced diet for space that meets the minimum World Health Organization (WHO) daily requirement composition of 15% protein, 30% lipids, and 55% carbohydrates can be achieved with a combination of starchy foods such as wheat, potatoes, sweet potatoes, rice, and protein-rich foods with good lipid profiles such as peanuts, soybeans, and dried beans.Salad ingredients including tomatoes, onions, spinach, beets, cabbage, carrots, lettuce and radishes can provide carbohydrates and essential minerals and vitamins. 6A number of these plants have been grown in space in small-scale experiments. 20Low gravity and radiation have impacts on bone and muscle loss, immune responses and oxidative stress, which essential nutrients and bioactive molecules in foods can help counteract. 6Appetite loss can be addressed with fresh food that offers a variety of tastes and textures and new plant varieties with distinct sensory profiles that encourage appetite.Food also has important social elements; familiarity, preparation and cooking can play an important role in wellbeing.Processing and storage to preserve nutrition and transform into familiar products (i.e., bread) will be a further challenge.Any combination of plants that provide the right nutritional balance will need to keep in mind psychological aspects -the food may be good for you, but unless it is appealing in taste, texture and smell, who will want to eat it?
Staple cereal crops such as wheat make up 70% of current diets but are challenging to grow in Space due to their larger size and breeding for outdoor growth.Early attempts to grow dwarf wheat varieties in growth modules on the Russian Space Station Mir had issues with excess ethylene due to gas compositions, leading to male sterility and no seed set. 32Advances in growth habitats and the use of 'super-dwarf' varieties to reduce the footprint have resulted in viable seed and tested canopy photosynthesis and respiration. 26,33Crop simulation models based on indoor wheat growth experiments propose a theoretical doubling of yield compared to the field grown with extended light to optimise photosynthesis, higher CO2 levels, no nutrient limitations or disease. 34Combined with the potential for continuous cropping independently of seasons, optimised wheat varieties for space may be a viable option in the future.In short, carbohydrates must come from alternative sources.6][37] These studies highlight the potential for tissue culture propagation of starch-rich tubers.Dietary fibre from carbohydrates also plays an important part in human health 38 and can be supplied by vegetables and salads.
The most extensively tested crops in space have been leafy greens/microgreens as they performed well in MODERN AGRICULTURE - 89 CEA, have compact size, potential for multiple cropping and large edible fraction. 39,40Red romaine lettuce and Chinese cabbage that produce healthy bioactive compounds such as antioxidants and essential dietary minerals 41 have been grown on the ISS.Chinese cabbage was shown to be sensitive to continuously elevated CO 2 in the Veggie system, which inhibited growth, highlighting the need for validation in space conditions. 42In addition to ISS, small Environmental Control and Life Support Systems hosted on a CubeSat plan to test autonomous growth from seed-to-seed of Micro-Tom, a dwarf tomato variety with a rapid life cycle, high fruit productivity and source of bioactive molecules such as carotenoids, anthocyanins and vitamins. 43 challenge will be identifying plants that can grow in space and provide sufficient protein and lipids.A candidate is duckweed, a small, extremely fast growing aquatic plant with desirable nutritional qualities.Duckweeds contain between 20% and 35% protein representing all essential amino acids, 4%-7% fats of which the majority are polyunsaturated fatty acids, and 4%-10% starch. 44Duckweed can maintain high photosynthetic capacity over a range of light conditions 45,46 making it highly suitable for CEA.Experiments to test duckweed growth in custom mG-Lilypond hydroponic chambers were included in the Blue Origin New Shepard Launch. 47In addition to being a healthy salad ingredient, duckweed has potential as a chassis for synthetic biology applications (discussed in 'New and Enhanced Functions'; 48 ).

THE IDEAL PLANT FORM FOR SPACE
It is useful to consider what the ideal plant form for growth in space settlements would be, given that we have the opportunity to decide which crops will be the focus of space agriculture research and development activities, and also given the opportunities that genetic engineering presents to modify the form of existing crops. 49The ideal plant form would resolve some of the challenges detailed above.Very limited physical space will be available.Plants that are compact and have a canopy structure that maximises photosynthesis and easy harvest will be most suitable.A harvest index (the ratio of harvested product to total plant biomass) close to 1 would be ideal.This might sound impossible initially, given that the harvest index traditionally considers the mass of fruit (or equivalent) as the product, but other plant organs are essential to fruit production.In space, the harvest index could be interpreted more broadly, with consideration given to alternative uses of non-food biomass, for example, in fibre or building materials.Nonetheless, biomass that will be less useful or entirely wasted should be reduced.Hydroponics or aeroponics is the nutrient delivery systems most likely to be used in space controlled environment agriculture, as the surface substrate (regolith) of the moon and Mars are a poor cultivation medium. 27,50Plants with reduced root biomass to minimise non-edible produce and with architecture optimised for nutrient and water delivery may include removal of fine root structures that could break off and block filtration and recycling in hydroponic systems.Plants with a short life cycle that yield all or most of the produce at the same time would ease harvesting and lend themselves to continuous cropping systems.Automated systems for harvesting that include sensors for detection and ripeness of produce will minimise labour and ensure picking at appropriate times. 22Overall, these needs are very closely aligned to the needs of the terrestrial vertical farming industry, on which space cultivation systems will be based. 51,52Vertical farming is particularly challenged by reliance on legacy crop cultivars, bred for the very different needs of traditional outdoor cropping systems.The development of new varieties more suited to controlled environment agriculture is an active area of research, encompassing both traditional breeding and more recent genetic modification and gene editing approaches. 49,53,54

SPACE PLANTS SHOULD HAVE NEW AND ENHANCED FUNCTIONS
Future space explorers would benefit if plants engineered for space encode a range of new functions, providing system resilience and resource efficiencies.Initial targets might include modifications or enhancements that assist plant growth and yield in a challenging space environment.Foremost amongst these will be the tolerance to stresses such as elevated radiation and altered gravity.The building settlement underground is one potential solution to this challenge.Nonetheless, given the uncertainty around the extent of radiation exposure that will be experienced and its effects, it would be prudent to expect that plant encoding some form of biological mitigation against radiation will be necessary.Performing experiments in space is extremely difficult and expensive.Ground analogues are frequently used to augment data from spaceflight, but are limited because they cannot truly replicate the space environment.As a result, the effects of space radiation on plant growth, development and yield are poorly understood. 55Enhancing antioxidant content in plants is one potential route to enhance plant radiation tolerance, with the dual benefit of providing additional dietary antioxidants and enhanced radiation tolerance to humans who might consume those plants. 56he performance of plants grown in space might also be improved by manipulating their gravity responses.Plants sense gravity through the movement of amyloplasts -plastids filled with starch granules. 57Amyloplasts move passively within cells, following the gravity vector they are exposed to. 58A polar signalling system, involving the LAZY1-LIKE family genes, is established in the plasma membrane at the point at which the amyloplasts settle. 591][62] Microgravity conditions, as experienced on the ISS or during space flight, alter many aspects of plant biology.For example, the development of reproductive organs is changed, and seeds produced in microgravity 90 -MODERN AGRICULTURE may have reduced potential to germinate. 12,13However, gravity on Mars and the moon is much greater than microgravity.The effects of long-term cultivation in a low gravity environment on plant growth and development are consequently poorly understood. 63It might be expected, however, that ideal space crops will require some augmentation of their gravity perception, either through enhanced sensitivity to gravity itself or by using other environmental signals that are more easily controlled, such as light. 63The gravitropic response varies both within and between species, and so the modifications necessary may vary similarly dependent upon the crop 64,65 It would be advantageous if new functions of plants for space also went beyond the immediate needs for growth and yield.Initial efforts might focus on the most mission-critical products, notably pharmaceuticals and vaccines.Availability of medical supplies will be a key challenge to the success of long-term space exploration. 66NASA expects that a complete Mars mission will take approximately 3 years, which may exceed the manufacturer's labelled expiration date of at least 87% of the medications stocked on the ISS. 66,67The space environment further complicates this issue.Data from medications onboard the ISS and from space-simulation experiments indicate that degradation and accumulation of contaminants may occur more rapidly than on Earth. 68,69This effect is, however, controversial, with other investigators arguing that it is the unusual packaging used during spaceflight that accelerates degradation and that this could be mitigated against by using the manufacturer's original packaging. 70Even given perfect storage conditions and shelf stability, taking a fully adequate pharmacy for all likely eventualities would be impossible owing to the vast range of possible needs in such a long-term mission.A predetermined pharmacy would also not account for emerging health risks, for example, an outbreak of a novel infectious disease.
Plant-based production of pharmaceuticals could support the acute and chronic health needs of space settlements.Plants are highly efficient biofactories, using light energy to produce biomass and a diverse array of primary and specialized metabolites.Several modern pharmaceuticals were initially derived from plant specialized metabolites (e.g., morphine and codeine from Papaver somniferum; aspirin from Salix spp.; atropine, scopolamine and hyoscyamine from Atropa belladonna). 71,72Whilst useful pharmaceutically active compounds might then be derived from plants grown in space settlements, two major issues present themselves.The first is that many of the relevant species are unsuitable for compact and intense indoor cultivation.Opium poppies, for example, are typically grown in broadacre cropping systems. 71The second major issue is that compounds currently available from plants would not provide anywhere near the complete necessary pharmacy for space settlement, because many modern pharmaceuticals are produced from partial or fully synthetic routes.Synthetic biology provides potential solutions to both these issues.
Plant synthetic biology and molecular farming (also 'pharming') are rapidly advancing research domains that seek to exploit plants to produce desired products.The goal is often either the generation of higher yields or efficiency than naturally possible, or to generate a product in a species where it is not normally found.Several examples exist already where plant metabolism has been reprogrammed to generate non-native biological products.4][75][76][77][78] A vast array of products is theoretically possible using plant synthetic biology, suggesting such approaches could be employed to meet the needs of space settlements. 79A plant synthetic biology chassis species might be selected, amenable to genetic engineering and rapid cultivation in the controlled environment systems expected to be used in space settlements.This would allow biotechnologists to specialize and become highly adept at modifying the plant's biochemical and physiological properties, and would remove the need to repeatedly modify plant form or environmental interactions to suit controlled environments.Duckweed is a strong candidate species for this role.It is a small, aquatic plant that grows very rapidly (doubling time 1-2 days) and in shallow water, with a relatively tractable genome. 80,81A recent NASA mission has tested the technology for duckweed cultivation in space. 47Complementary microbial-based synthetic biology solutions would likely also be used, but plant systems offer the advantage of having membrane compartments that are needed for the expression of some biosynthetic enzymes and which microbes lack. 82The synthetic biology approaches applied for pharmaceuticals and medical products could be used for other products necessary for life support, assuming that the relevant pathway can be engineered into the chassis plant.

APPROACHES TO CREATING AND IMPROVING PLANTS FOR SPACE
Several complementary approaches will be taken to generate plants with ideal characteristics for space, building upon current efforts by on-Earth CEA and agricultural biotechnology.Careful study and thorough understanding of the influence of environmental conditions is perhaps the easiest tool available.This would include light conditions, nutrient supply, and cropping practices such as density.This need for precise environmental control makes vertical farming systems the most suitable current CEA technology that could be adapted for crop production in space settlements.Lighting conditions are a key factor that can be optimised to allow stable growth and yield as they influence photosynthetic efficiency. 835][86] Altering the ratios of blue and red light from LED illumination affects the development of leafy greens and primary growth in tomato. 86,87Exploring the response of lettuce to seven different LED 'light recipes' including blue, red and farred light in growth chambers showed that certain wavelengths could increase biomass at distinct stages of the growth cycle, as well as impact morphology, secondary metabolites and nutrients. 88Advanced CEA systems would also allow the control of CO 2 , which can increase plant growth, and the recycling of water and nutrients via hydroponics or aeroponics to enhance resource efficiency. 84However, tests of cultivation methods must be carried out, examining solid growth media, hydroponics, aquaponics and aquaponics, to identify the option offering the greatest yield combined with practical utility in the space environment.Together, these approaches will assist in manipulating plant growth rate and yield.
There are limits to the extent of crop improvement that can be achieved through environmental manipulation alone.The genetics of the available crops are also key to yield and performance in any cropping system.Currently only a limited number of crops are grown commonly in vertical farms, primarily lettuce and other leafy greens, herbs and microgreens because they already exhibit traits that are highly compatible with vertical farming systems. 51,53However, other crops are thought to be quite suitable, such as tomatoes because they have already been adapted to cultivation in protected cropping systems that have similarities to vertical farming, and strawberries due to their compact size.Natural genetic diversity is an excellent resource to find traits within a species that could improve performance in vertical farming systems. 89Therefore, one of the earliest aims for SpaceAg development would be to exploit existing natural genetic diversity and develop breeding programs to combine useful traits.Tomatoes are an appealing early target species.1][92] For any target species, high-throughput phenotyping will help to identify the varieties with the best yield/size ratio and monitor the production, which would be a first step towards culture automation. 93,94odern gene editing and genetic modification technologies will also contribute to developing crops suitable for SpaceAg.Previously, stable transformation with complete gene constructs to drive some desirable trait or phenotypic change was the most common approach to genetic modification. 95More recently, CRISPR-Cas gene editing systems have begun to offer greater precision and versatility, lending themselves to a wide range of applications. 96Gene editing methods are advantageous because they offer the ability to make precise nucleotide sequence changes and deletions at specifically targeted locations in the genome, allowing individual genes to be modified or deleted.1][102] New architectures can also be achieved by modification of specific genes, such as a tomato variety with a shorter stem combined with condensed shoots and rapid flowering, and a dwarf rice variety generated by disruption of gibberellin signalling. 49,103uality traits can also be improved, such as in a wheat variety where amylopectin content was increased to improve digestibility and offer health benefits. 104,105RISPR technologies can also create a continuum of variation when they target the regulatory region of a gene of interest, resulting in the expression of diverse cis-regulatory alleles and therefore offspring with a spectrum in quantitative yield-related traits, suitable for subsequent breeding and selection. 106All of these gene editing, genetic modification and transformation techniques will also be harnessed to generate synthetic biology solutions for SpaceAg, ranging from precise manipulation of individual enzyme specificity to tailor the output of existing plant biochemical pathways, such as the manipulation of biochemicals, to the introduction of complete new metabolic pathways. 79

APPLICATIONS OF SPACEAG ON EARTH
Our food supply on Earth is challenged by many factors including the continual increase in the world population, climate change, land degradation and overuse of pesticides, and emerging threats to the recent coronavirus pandemic.Climate change is at the forefront, severely threatening food production essentially everywhere.More frequent extreme weather events such as droughts, floods and bushfires have fuelled a debate about the climate crisis and what can be done to prepare ourselves. 8The innovations and solutions that emerge from SpaceAg can be a valuable resource in this crisis. 107The techniques and tools developed to grow crops in the resource-scarce environments of space can be translated to tackle similar challenges on Earth.Such techniques might involve alternative growth media, optimising nutrient delivery, or select plant varieties with enhanced stress tolerance.The principles that drive SpaceAg, such as efficient resource use and closed-loop systems, can guide the development of resilient agricultural models on Earth, which can mitigate some of the aforementioned challenges, supporting both food security and sustainability (Figure 2).
Regions with limited resources or challenging environments can benefit especially from SpaceAg's discoveries.9][110] In the case of Singapore, a lack of suitable land for agriculture is the primary challenge, whilst in the Middle East, water availability and soil quality are the most 92 -MODERN AGRICULTURE significant issues.This mirrors key challenges for plant cultivation in space.Present terrestrial CEA systems are often energy-intensive, resource-hungry, and rarely profitable. 111SpaceAg can contribute to the step change needed in their design and optimisation.Both biological technologies and engineering solutions developed for space might be deployed to support Earth-based CEAs.3][114] Furthermore, portable, and spaceefficient CEA units designed using SpaceAg technologies could be used as emergency food production units on Earth.These units can be deployed in disaster-hit areas to ensure a continuous supply of fresh produce until traditional agriculture can be re-established.
Innovations in plant synthetic biology driven by space will, in many cases, be equally applicable on Earth.For example, duckweed synthetic biology systems that produce pharmaceuticals at high-yield and low-cost could be scaled up to provide for demand on Earth. 80,81nergy-efficient CEA systems developed to cultivate F I G U R E 2 Applications of SpaceAg on Earth.The benefits and applications that can be derived from SpaceAg research include plants as biofactories to synthesise valuable compounds, proteins and materials, plants as a source of medicine production system to produce novel or enhanced medicinal compounds, innovations in CEA technologies promoting sustainable and efficient food production in regions with high population, limited resources or in remote areas on Earth, and new technologies aiding in the development of crops capable of tolerating suboptimal conditions (extreme temperatures, water and nutrient deficient conditions) on Earth.
MODERN AGRICULTURE duckweed in space could be adapted as sterile biofactories on Earth.This may contribute to the cheaper biomanufacturing of life-saving drugs that are otherwise prohibitively expensive to produce. 115With further innovation, bioengineered aquatic plants like duckweed could change access to essential medicines in developing countries, providing economic and health benefits across the world.While the full potential is yet to be realised, plants engineered as molecular pharming factories for space represent a transformative opportunity for increasing the global supply of pharmaceuticals and enabling healthcare equity on Earth. 116

CONCLUSIONS
More than 50 years after the first mission to land on the moon, space exploration has reached a point where habitation on the moon and Mars is conceivable.In this review, we have discussed the optimisation of plant growth for sustainable SpaceAg, encompassing current and future space crops, their ideal form, and improved functions.Vertical farming is the best option for growing plants in space to reduce the effects of radiation and temperature extremes and for sustainable use of resources.There is a wealth of opportunity to engineer plants for CEA conditions and tune conditions for optimal growth and novel traits.Improvements in plants include size and stature to maximise light exposure, synchronised growth, and fruit ripening with harvestable index of 1. Optimisation of growth environments will include lighting regimes, temperature and gas control, water, and nutrient delivery.Different cultivated plant species vary in response to the same conditions, meaning that the range of crops needed to provide full nutrition in space must be designed accordingly.]117 By 2050, nearly 10 billion people on Earth will need to be fed with sustainable nutritious food, grown in potentially challenging environments.Approaches to optimise the crop production for SpaceAg can have benefits for Earth-sustainability, in particular because CEA farming systems consume little water and land, and are potentially free of pesticides and added nutrients. 51Technological advances in engineering and plant breeding needed to support life off-Earth therefore have great potential to support better health and environmental outcomes on-Earth.