Combined Environmental Stress Responses and Their Influence on Bacterioruberin Biosynthesis: A Comprehensive Review
DOI:
https://doi.org/10.5281/zenodo.18375548Keywords:
Bacterioruberin, Haloarchaea, Hypersaline stress, Oxidative stress, pH, Carotenoid biosynthesis, Nutrient limitation, Stress synergyAbstract
Haloarchaea inhabit hypersaline environments that impose multiple stresses, including extreme salinity, intense solar radiation, temperature fluctuations, oxidative stress and nutrient scarcity. These extremophilic archaea have evolved unique adaptations such as the salt in strategy, hyperacidic proteins and the production of the rare C₅₀ carotenoid bacterioruberin (BR). BR stabilizes membranes, scavenges reactive oxygen species and shields cells against ultraviolet light. Understanding how combined environmental stresses influence BR biosynthesis is essential for optimizing its biotechnological production and for elucidating haloarchaeal stress physiology. This review synthesizes literature from 2000-2025 on haloarchaeal stress responses and BR regulation. Firstly, discussed the biochemical properties and functions of BR, then examine the individual effects of salinity, light intensity, temperature, oxidative stress, nutrient limitation and pH on BR production. Studies show that high salinity (12―25 % NaCl) and moderately alkaline pH (ca. 8–9) favour haloarchaeal growth, but BR accumulation is maximized under moderate salinity (∼12.5 %), nutrient limitation, low carbon to nitrogen ratios and oxidative or photooxidative stress. Light stimulates carotenoid biosynthesis in some species but not others. Synergistic and antagonistic interactions among stresses and summarize molecular regulation of BR biosynthesis were analysed, highlighting the crtD/lyeJ/cruF gene cluster and stress responsive regulators like RosR. Although numerous studies optimise individual parameters, few systematically evaluate multi factor stress interactions. Meta synthesis reveals common trends and methodological limitations, guiding future research. Finally, biotechnological strategies to enhance BR production were explored and propose future research directions in systems biology and synthetic biology.
References
Baati, H., Siala, M., Azri, C., Ammar, E., & Trigui, M. (2022). Hydrolytic enzyme screening and carotenoid production evaluation of halophilic archaea isolated from highly heavy metal-enriched solar saltern sediments. Brazilian Journal of Microbiology, 53(4), 1893–1906. https://doi.org/10.1007/s42770-022-00855-6
Cho, E.-S., Hwang, C. Y., & Seo, M.-J. (2024). Optimized production of bacterioruberin from Haloferax marinum using one-factor-at-a-time and central composite design approaches. Bioresources and Bioprocessing, 11(1), Article 111. https://doi.org/10.1186/s40643-024-00834-9
Couto-Rodríguez, R. L., Koh, J., Chen, S., & Maupin-Furlow, J. A. (2023). Insights into the lysine acetylome of the haloarchaeon Haloferax volcanii during oxidative stress by quantitative SILAC-based proteomics. Antioxidants, 12(6), Article 1203. https://doi.org/10.3390/antiox12061203
Flores, N., Hoyos, S., Venegas, M., Galetović, A., Zúñiga, L. M., Fábrega, F., Paredes, B., Salazar-Ardiles, C., Vilo, C., Ascaso, C., Wierzchos, J., Souza-Egipsy, V., Araya, J. E., Batista-García, R. A., & Gómez-Silva, B. (2020). Haloterrigena sp. strain SGH1, a bacterioruberin-rich, perchlorate-tolerant halophilic archaeon isolated from halite microbial communities, Atacama Desert, Chile. Frontiers in Microbiology, 11, Article 324. https://doi.org/10.3389/fmicb.2020.00324
Giani, M., Garbayo, I., Vílchez, C., & Martínez-Espinosa, R. M. (2019). Haloarchaeal carotenoids: Healthy novel compounds from extreme environments. Marine Drugs, 17(9), Article 524. https://doi.org/10.3390/md17090524
Giani, M., Gervasi, L., Loizzo, M. R., & Martínez-Espinosa, R. M. (2022). Carbon source influences antioxidant, antiglycemic, and antilipidemic activities of Haloferax mediterranei carotenoid extracts. Marine Drugs, 20(11), Article 659. https://doi.org/10.3390/md20110659
Giani, M., Montero-Lobato, Z., Garbayo, I., Vílchez, C., Vega, J. M., & Martínez-Espinosa, R. M. (2021). Haloferax mediterranei cells as C50 carotenoid factories. Marine Drugs, 19(2), Article 100. https://doi.org/10.3390/md19020100
Haque, R. U., Paradisi, F., & Allers, T. (2020). Haloferax volcanii for biotechnology applications: Challenges, current state and perspectives. Applied Microbiology and Biotechnology, 104(4), 1371–1382. https://doi.org/10.1007/s00253-019-10314-2
Hwang, C. Y., Cho, E. S., Rhee, W. J., Kim, E., & Seo, M. J. (2022). Genomic and physiological analysis of C50 carotenoid-producing novel Halorubrum ruber sp. nov. Journal of Microbiology, 60(10), 1007–1020. https://doi.org/10.1007/s12275-022-2173-1
Jones, D. L., & Baxter, B. K. (2017). DNA repair and photoprotection: Mechanisms of overcoming environmental ultraviolet radiation exposure in halophilic archaea. Frontiers in Microbiology, 8, Article 1882. https://doi.org/10.3389/fmicb.2017.01882
Ma, Y., Sun, Z., Yang, H., Xie, W., Song, M., Zhang, B., & Sui, L. (2024). The biosynthesis mechanism of bacterioruberin in halophilic archaea revealed by genome and transcriptome analysis. Applied and Environmental Microbiology, 90(7), e00540-24. https://doi.org/10.1128/aem.00540-24
Martínez-Espinosa, R. M. (2025). Bacterioruberin (C50 carotenoid): Nutritional and biomedical potential of a microbial pigment. Nutrients, 17(24), Article 3899. https://doi.org/10.3390/nu17243899
Matarredona, L., Camacho, M., Zafrilla, B., Bonete, M.-J., & Esclapez, J. (2020). The role of stress proteins in haloarchaea and their adaptive response to environmental shifts. Biomolecules, 10(10), Article 1390. https://doi.org/10.3390/biom10101390
Montero-Lobato, Z., Ramos-Merchante, A., Fuentes, J. L., Sayago, A., Fernández-Recamales, Á., Martínez-Espinosa, R. M., Vega, J. M., Vílchez, C., & Garbayo, I. (2018). Optimization of growth and carotenoid production by Haloferax mediterranei using response surface methodology. Marine Drugs, 16(10), Article 372. https://doi.org/10.3390/md16100372
Moopantakath, J., Imchen, M., Anju, V. T., Busi, S., Dyavaiah, M., Martínez-Espinosa, R. M., & Kumavath, R. (2023). Bioactive molecules from haloarchaea: Scope and prospects for industrial and therapeutic applications. Frontiers in Microbiology, 14, Article 1113540. https://doi.org/10.3389/fmicb.2023.1113540
Palanisamy, M., & Ramalingam, S. (2024). Microbial bacterioruberin: A comprehensive review. Indian Journal of Microbiology, 64(4), 1477–1501. https://doi.org/10.1007/s12088-024-01312-8
Sharma, K., Gillum, N., Boyd, J. L., & Schmid, A. (2012). The RosR transcription factor is required for gene expression dynamics in response to extreme oxidative stress in a hypersaline-adapted archaeon. BMC Genomics, 13, Article 351. https://doi.org/10.1186/1471-2164-13-351
Vázquez-Madrigal, A. S., Barbachano-Torres, A., Arellano-Plaza, M., Kirchmayr, M. R., Finore, I., Poli, A., Nicolaus, B., De la Torre Zavala, S., & Camacho-Ruiz, R. M. (2021). Effect of carbon sources in carotenoid production from Haloarcula sp. M1, Halolamina sp. M3 and Halorubrum sp. M5, halophilic archaea isolated from Sonora saltern, Mexico. Microorganisms, 9(5), Article 1096. https://doi.org/10.3390/microorganisms9051096
Yang, Y., Yatsunami, R., Ando, A., Miyoko, N., Fukui, T., Takaichi, S., & Nakamura, S. (2015). Complete biosynthetic pathway of the C50 carotenoid bacterioruberin from lycopene in the extremely halophilic archaeon Haloarcula japonica. Journal of Bacteriology, 197(9), 1614–1623. https://doi.org/10.1128/JB.02523-14
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Devi Prasad Panda

This work is licensed under a Creative Commons Attribution 4.0 International License.