INTERNATIONAL CONGRESS OF
PharmacoGenetics
Synthetic Epigenetic Engineering of Extremophilic Bacteria: Prospects for Biotechnological and Space Applications
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Shirin Dehghan,1,*
1. Genetics graduate, Kharazmi University
- Introduction: Extremophilic bacteria possess extraordinary resilience to environmental stressors, including high radiation, desiccation, temperature extremes, and oxidative damage, making them prime candidates for biotechnological exploitation and astrobiological studies. Recent advances in synthetic biology and epigenetic engineering have opened avenues to modulate microbial stress responses with unprecedented precision, allowing the design of extremophiles with tailored traits for industrial, environmental, and space applications. This review synthesizes current progress in the synthetic epigenetic engineering of extremophilic bacteria and explores its translational potential.
- Methods: Synthetic epigenetic engineering involves deliberate modification of DNA methylation patterns, histone-like protein states, and regulatory RNA networks to control gene expression dynamically without altering the genomic sequence. In extremophiles such as Deinococcus radiodurans and Thermus thermophilus, DNA methylation is tightly linked to the regulation of DNA repair genes and oxidative stress response operons. Emerging CRISPR-dCas9-based epigenetic editors allow site-specific recruitment of methyltransferases or demethylases to target loci, enabling reversible modulation of stress-response genes. For example, targeted methylation of the recA promoter in D. radiodurans can enhance or suppress homologous recombination pathways, optimizing radiation tolerance for specific applications. Histone-like nucleoid-associated proteins (NAPs), such as HU, IHF, and Lrp, can also be engineered using synthetic biology approaches to modulate chromatin-like structures in prokaryotes. Post-translational modification mimetics, fusion with synthetic effector domains, or inducible expression systems can alter nucleoid compaction, DNA accessibility, and transcriptional dynamics, thereby enhancing survival under extreme thermal or oxidative conditions. In thermophiles, such modulation has demonstrated improved enzymatic stability, enabling their use in high-temperature industrial bioprocesses.
- Results: Non-coding RNAs (ncRNAs) provide a rapid and reversible regulatory layer that can be synthetically tuned. Engineered small RNAs and riboswitches can target stress-response transcripts, creating programmable feedback circuits that respond to environmental signals such as UV flux or nutrient limitation. For instance, synthetic ncRNA circuits in halophiles have been designed to upregulate compatible solute biosynthesis under osmotic stress, improving biomass accumulation and metabolite production in high-salinity bioreactors. The translational potential of synthetic epigenetic engineering in extremophiles is significant. In biotechnological contexts, engineered extremophiles can produce heat-stable enzymes, biofuels, and bioplastics under harsh conditions that would limit conventional microbial production systems. In space applications, epigenetically tuned microbes could serve as self-sustaining life support components, performing in situ resource utilization, bioremediation, or bio-manufacturing on extraterrestrial surfaces with high radiation, vacuum, and low temperature. Despite the promise, challenges remain. Epigenetic modifications in extremophiles are context-dependent and often influenced by multi-layered regulatory networks, complicating predictive engineering. Additionally, the long-term stability of synthetic epigenetic states under space-like conditions is not fully understood. Integration of multi-omics approaches, high-throughput screening, and AI-driven predictive modeling is crucial for rational design and optimization of engineered strains. Regulatory considerations for release and utilization in extraterrestrial or terrestrial environments also require careful ethical and biosafety assessment.
- Conclusion: In conclusion, synthetic epigenetic engineering represents a transformative approach to harnessing extremophilic bacteria for biotechnological innovation and space exploration. By precisely modulating DNA methylation, nucleoid architecture, and RNA-mediated regulatory networks, engineered extremophiles can be tailored for enhanced stress resistance, metabolite production, and adaptive performance in extraterrestrial environments. Future research combining CRISPR-based epigenetic tools, computational modeling, and spaceflight experiments will be pivotal to realizing the full potential of this emerging interdisciplinary frontier.
- Keywords: Extremophilic Bacteria, DNA Methylation, CRISPR-dCas9, Nucleoid-associated Proteins
