MOF-encased ‘living seeds’ could enable engineered microbes for manufacturing, medicine, and beyond


Dec 19, 2023 (Nanowerk Spotlight) Genetically engineered microbes hold astonishing potential as living factories, diagnostic tools, environmental cleansers, and beyond. Yet for all their promise, these organisms remain largely confined to carefully controlled laboratory settings, unable to thrive amid the variable conditions of natural and industrial habitats. The fragility of engineered cells has severely limited their real-world impact across the manufacturing, healthcare, sustainability, and space exploration spheres where microbial solutions could drive immense progress. Now, an ingenious biohybrid material developed by researchers at prominent Chinese institutions finally provides a means to sturdily encapsulate modified microbes for sheltered transport and selective release. Their so-called “living seeds” integrate hardy bacterial spores inside protective shells built from metal-organic frameworks, a highly adaptable class of crystalline porous materials. This specialized vessels safeguard designer microbes from environmental assaults, grant precise control over organism deployment, and could launch a new era where genetically enhanced microbes journey forth to reshape reality. The researchers published their findings in Advanced Materials (“Living Seed Materials Made by Metal–Organic Framework-Encapsulated Bacillus Subtilis Spore”). By encapsulating genetically modified Bacillus subtilis spores inside metal-organic framework (MOF) shells, the researchers created “living seed” particles that protect microbes in hostile conditions while allowing controlled release into growth media. This breakthrough tackles a longstanding barrier for genetically modified organism (GMO) technologies, which tend to perform well in the lab but struggle in unpredictable real-world environments. A schematic showing the design of living seed materials inspired by the growth of a giant tree from a plant seed A schematic showing the design of living seed materials inspired by the growth of a giant tree from a plant seed. a) The life cycle of a plant seed of a natural material; the endosperm of angiosperm plants forms a core–shell structure of kernel surrounding a nutshell during seed development. In desirable nutrient-rich environments, the seed can grow into a giant tree. b) Taking inspiration of a plant seed, the development of MOF-encapsulated spore as living seed material is proposed. The spores of engineered bacteria can be encapsulated into a ZIF-8 core–shell structure. Once fabricated, this living seed material can respond to specific environmental conditions and release the spores, which then eventually germinate into functional living bacteria with pre-designed features. (Reprinted with permission by Wiley-VCH Verlag) The inspiration for the living seeds came from nature. Plant seeds contain protective outer coatings that shield embryo tissues from stresses like drought and UV radiation until conditions become ripe for germination. The researchers aimed to recreate this adaptive mechanism using MOFs, a highly customizable class of porous materials formed from metal nodes bridged by organic linker molecules. MOFs possess useful properties like high surface area, structural integrity, and environmental responsiveness. These characteristics made MOFs attractive vessels for housing genetically engineered B. subtilis spores with advanced functions programmed into their DNA. B. subtilis spores were selected due to their hardiness and ability to reanimate as vegetative bacteria when nourished. By expressing fluorescent reporter proteins in the spores, the team could visually track spore-to-bacteria transitions. The living seed production process entailed suspending spores and metal ions in tiny water droplets, emulsifying the aqueous phase in oil, then precipitating a porous ZIF-8 MOF shell around each droplet. This yielded uniform, hollow microspheres with spores contained in the interior void space. The spheres protected internal spores during harsh treatments like high heat, oxidative bleach, and UV irradiation that destroyed unshielded spores. ZIF-8 degradation rates depended on surrounding media, enabling controlled nutrient-triggered spore release. Released spores successfully matured into functional engineered bacteria when incubated in growth media. As demonstrations, the researchers prepared living seeds harboring B. subtilis designed to sense the chemicals IPTG and cuminic acid. Post-release, bacteria regained responsiveness to target chemicals at sensitivity thresholds comparable to non-encapsulated counterparts. Such environmentally controlled preservation and revival of engineered microbes holds exciting possibilities for microbial technologies presently confined to controlled settings like factories and labs. By granting enhanced resilience, living seed vessels could permit functional GMOs to fulfill roles in unpredictable locales such as the human gastrointestinal system, contaminated water supplies, and even extraterrestrial terrain if spore-laden spacecraft reach other worlds. Additionally, the living seed concept should generalize to other microorganism types amendable to genetic modification and sporulation. The research represents a breakthrough marriage of synthetic biology and materials science. Living seed platforms stand to benefit emerging applications of engineered microbes across manufacturing, therapeutics, environmental management, and space exploration domains. As lead author Dr. Chao Zhong concludes, “[This] encourages further exploration into diverse MOF designs and applications… Moreover, innovative functional genetic circuits can be conceived for additional applications of biosensors.” It seems only a matter of time before organisms enhanced by living seed encasement exit the lab for adventurous destinations as heralds of engineered life’s expanding domain.


Michael Berger
By
– Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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