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Bio-Technology Readiness Levels (B-TRLs) of archaeal cell factories. This figure is a depiction of the cell factory producing the various products analysed through this review and shows their currect B-TRLs. This image has been designed using resources from Freepik.com.
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Archaea are a domain of prokaryotic organisms with intriguing physiological characteristics and ecological importance. In Microbial Biotechnology, archaea are historically overshadowed by bacteria and eukaryotes in terms of public awareness, industrial application, and scientific studies, although their biochemical and physiological properties show...
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Context 1
... the production of many compounds within the archaea was significantly improved by genetic engineering. To date, only a few companies are working on archaeal cell factories and commercialization is limited to halophilic archaea producing high value products with a growing market demand such as bacterioruberin, ether lipids, and various isoprenoids (Fig. ...
Context 2
... this cultivation, biomass was first produced under optimal growth conditions, after which the cells were transferred to a hypoosmotic medium optimized for bacterioruberin production. This increased the production 6.4-fold from 0.095 A 494nm mL 1 broth to 0.604 A 494nm mL 1 broth (Fang et al., 2010). Although increasing yield, this process also increased the number of cultivation steps, thus increasing the amount of work needed for the production. ...
Citations
... coli and Saccharomyces cerevisiae (2). Nevertheless, recent studies have revealed that halophilic microorganisms are promising for the next-generation microbial cell factory (1,2). ...
... coli and Saccharomyces cerevisiae (2). Nevertheless, recent studies have revealed that halophilic microorganisms are promising for the next-generation microbial cell factory (1,2). Among them, the halophilic archaea are advantageous as microbial cell factories. ...
Halophilic archaea are promising microbial cell factories for bacterioruberin (BR) production. BR is a natural product with multi-bioactivities, allowing potential application in many fields. In the previous work, a haloarchaeon Halorubrum sp. HRM-150 with a high proportion of BR (about 85%) was isolated, but the low yield impeded its large-scale production. This work figured out BR synthesis characteristics and mechanisms, and proposed strategies for yield improvement. First, glucose (10 g/L) and tryptone (15 g/L) were tested to be better sources for BR production. Besides, the combination of glucose and starch achieved the diauxic growth, and the biomass and BR productivity increased by 85% and 54% than using glucose. Additionally, this work first proposed the BR synthesis pattern, which differs from that of other carotenoids. As a structural component of cell membranes, the BR synthesis is highly coupled with growth, which was most active in the logarithm phase. Meanwhile, the osmotic down shock at the logarithm phase could increase the BR productivity without sacrificing the biomass. Moreover, the de-novo pathway for BR synthesis with a key gene of lyeJ , and its competitive pathways (notably tetraether lipids and retinal) were revealed through genome, transcriptome, and osmotic down shock. Therefore, the BR yield is expected to be improved through mutant construction, such as the overexpression of key gene lyeJ and the knockout of competitive genes, which need to be further explored. The findings will contribute to a better understanding of the metabolism mechanism in haloarchaea and the development of haloarchaea as microbial cell factories.
IMPORTANCE
Recent studies have revealed that halophilic microorganism is a promising microbial factory for the next-generation industrialization. Among them, halophilic archaea are advantageous as microbial factories due to their low contamination risk and low freshwater consumption. The halophilic archaea usually accumulate long chain C 50 carotenoids, which are barely found in other organisms. Bacterioruberin (BR), the major C 50 carotenoid, has multi-bioactivities, allowing potential application in food, cosmetic, and biomedical industries. However, the low yield impedes its large-scale application. This work figured out the BR synthesis characteristics and mechanism, and proposed several strategies for BR yield improvement, encouraging halophilic archaea to function as microbial factories for BR production. Meanwhile, the archaea have special evolutionary status and unique characteristics in taxonomy, the revelation of BR biosynthesis mechanism is beneficial for a better understanding of archaea.
... Their metabolism is versatile thanks to molecular adaptations to extreme conditions in terms of environmental parameters or nutrient availability. Additionally, they produce other biomolecules with high biotechnological interest, like carotenoids (Flemming, 2016;Giani et al., 2019;Giani et al., 2022;Giani et al., 2021;Pfeifer et al., 2021) and exopolysaccharides (Flemming, 2016;Costa et al., 2018;Blackburn and Green, 2022). Besides, some haloarchaea can be used in the bioremediation processes to remove heavy metals and inorganic anions from brines and salty water (Oren, 2010;Nájera-Fernández et al., 2012;Martínez-Espinosa et al., 2015;Hou and Cui, 2018;Zuo et al., 2018;Pacholak et al., 2021;Pfeifer et al., 2021;Martínez et al., 2022;Moopantakath et al., 2023). ...
... Additionally, they produce other biomolecules with high biotechnological interest, like carotenoids (Flemming, 2016;Giani et al., 2019;Giani et al., 2022;Giani et al., 2021;Pfeifer et al., 2021) and exopolysaccharides (Flemming, 2016;Costa et al., 2018;Blackburn and Green, 2022). Besides, some haloarchaea can be used in the bioremediation processes to remove heavy metals and inorganic anions from brines and salty water (Oren, 2010;Nájera-Fernández et al., 2012;Martínez-Espinosa et al., 2015;Hou and Cui, 2018;Zuo et al., 2018;Pacholak et al., 2021;Pfeifer et al., 2021;Martínez et al., 2022;Moopantakath et al., 2023). Within haloarchaea, the most promising microorganism is Haloferax mediterranei (Pfeifer et al., 2021;Hagagy et al., 2022;Costa et al., 2023;Diankristanti et al., 2023), because it can synthesize PHBV without using any HV precursor (as required by other microorganisms) and can use different carbon sources to accomplish it (Tan et al., 2014b;Han et al., 2015;Parroquin-Gonzalez and Winterburn, 2023). ...
... Besides, some haloarchaea can be used in the bioremediation processes to remove heavy metals and inorganic anions from brines and salty water (Oren, 2010;Nájera-Fernández et al., 2012;Martínez-Espinosa et al., 2015;Hou and Cui, 2018;Zuo et al., 2018;Pacholak et al., 2021;Pfeifer et al., 2021;Martínez et al., 2022;Moopantakath et al., 2023). Within haloarchaea, the most promising microorganism is Haloferax mediterranei (Pfeifer et al., 2021;Hagagy et al., 2022;Costa et al., 2023;Diankristanti et al., 2023), because it can synthesize PHBV without using any HV precursor (as required by other microorganisms) and can use different carbon sources to accomplish it (Tan et al., 2014b;Han et al., 2015;Parroquin-Gonzalez and Winterburn, 2023). The metabolic pathways that allow the production of PHA are diverse if they are analyzed and compared in all groups of microorganisms, but essentially, all of them share the following reactions. ...
Global concern about plastic pollution is forcing new policies and modifications of human consumption as well as promoting new research lines aiming at the replacement of non-degradable plastics with other polymers more environmentally friendly. Addressing food waste and promoting circular economy strategies, among other approaches, are crucial in reducing environmental impacts and fostering sustainability in several sectors like the agri-food industry. The European Union’s Circular Economy Action Plan is a significant initiative in this direction. Biotechnological processes, especially the valorisation of agri-food waste to produce highly marketed biomolecules like poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) using microorganisms as cellular factories, offer promising avenues for achieving these goals. PHBV is a biodegradable polymer firstly characterised as an isolated biopolymer from bacterial biomass. This biopolymer shows interesting physicochemical properties making possible immense potential in various applications due to its biocompatibility and sustainability, thus revealing it as a good candidate to replace plastics produced by chemical synthesis from petroleum (which are highly recalcitrant and consequently pollutants). This review critically analyses the PHBV synthesis and end-of-life scenarios from their synthesis using chemical and biological pathways, through the forms of biotechnological operation and production, to the forms described until the moment of recycling.
... A search was conducted on the Web of Science, PubMed, Embase, and Scopus databases using MeSH descriptors and keywords related to technology readiness levels (TRLs) in pharmaceutical development, identifying 360 references. After removing duplicates, 262 articles were analyzed, and 12 were selected for further consideration based on the specific mention of TRL in any biological field [40,[136][137][138][139][140][141][142][143][144][145][146]. None specifically addressed TRLs in pharmaceutical development, including small molecules, biotechnological products, and herbal medicinal products (HMPs) for human use. ...
Despite the vast global botanical diversity, the pharmaceutical development of herbal medicinal products (HMPs) remains underexploited. Of over 370,000 described plant species, only a few hundred are utilized in HMPs. Most of these have originated from traditional use, and only a minority come from megadiverse countries. Exploiting the pharmacological synergies of the hundreds of compounds found in poorly studied plant species may unlock new therapeutic possibilities, enhance megadiverse countries’ scientific and socio-economic development, and help conserve biodiversity. However, extensive constraints in the development process of HMPs pose significant barriers to transforming this unsatisfactory socio-economic landscape. This paper proposes a roadmap to overcome these challenges, based on the technology readiness levels (TRLs) introduced by NASA to assess the maturity of technologies. It aims to assist research entities, manufacturers, and funding agencies from megadiverse countries in the discovery, development, and global market authorization of innovative HMPs that comply with regulatory standards from ANVISA, EMA, and FDA, as well as WHO and ICH guidelines.
... In this context, new natural biomaterials such as archaeolipids are being explored with growing interest in the drug delivery field [27,28]. Nanoarchaeosomes (nanoARC) prepared with lipids extracted from H. tebenquichense, for example, are naturally targeted to scavenger receptor A I/II (SRAI/II) expressed by phagocytic cells and certain endothelial cells and outperform liposomes in structural simplicity and resistance to mechanical stress. ...
Sodium alendronate (ALN) is a very hydrosoluble and poorly permeable molecule used as an antiresorptive agent and with vascular anticalcifying capacity. Loaded into targeted nanovesicles, its anti-inflammatory activity may be amplified towards extra-osseous and noncalcified target cells, such as severely irritated vascular endothelium. Here cytotoxicity, mitochondrial membrane potential, ATP content, and membrane fluidity of human endothelial venous cells (HUVECs) were determined after endocytosis of ALN-loaded nanoarchaeosomes (nanoARC-Chol(ALN), made of polar lipids from Halorubrum tebenquichense : cholesterol 7:3 w/w, 166 ± 5 nm, 0.16 ± 0.02 PDI, −40.8 ± 5.4 mV potential, 84.7 ± 21 µg/mg ALN/total lipids, TL). The effect of nanoARC-Chol(ALN) was further assessed on severely inflamed HUVECs. To that aim, HUVECs were grown on a porous barrier on top of a basal compartment seeded either with macrophages or human foam cells. One lighter and one more pronounced inflammatory context was modelled by adding lipopolysaccharide (LPS) to the apical or the apical and basal compartments. The endocytosis of nanoARC-Chol(ALN), was observed to partly reduce the endothelial-mesenchymal transition of HUVECs. Besides, while 10 mg/mL dexamethasone, 7.6 mM free ALN and ALN-loaded liposomes failed, 50 μg/mL TL + 2.5 μg/mL ALN (i.e., nanoARC-Chol(ALN)) reduced the IL-6 and IL-8 levels by, respectively, 75% and 65% in the mild and by, respectively, 60% and 40% in the pronounced inflammation model. This is the first report showing that the endocytosis of nanoARC-Chol(ALN) by HUVECs magnifies the anti-inflammatory activity of ALN even under conditions of intense irritation, not only surpassing that of free ALN but also that of dexamethasone.
... attractive for industrial bioproduction of methane, as well as amino acids (Pappenreiter et al., 2019;Pfeifer et al., 2021;Taubner et al., 2023). ...
... Archaea constitute a domain of prokaryotic organisms found in almost every habitat on the planet. Some have adapted to survive in extreme environmental conditions [1]. These extreme environments are characterized by high (T > 70 • C) or low (T < 0 • C) temperatures, high alkalinity (pH > 10) or acidity (pH < 5) and high salinities (NaCl concentration greater than 10%) [2]. ...
Only a few halophilic archaea producing carboxylesterases have been reported. The limited research on biocatalytic characteristics of archaeal esterases is primarily due to their very low production in native organisms. A gene encoding carboxylesterase from Halobacterium salinarum NRC-1 was cloned and successfully expressed in Haloferax volcanii. The recombinant carboxylesterase (rHsEst) was purified by affinity chromatography with a yield of 81%, and its molecular weight was estimated by SDS-PAGE (33 kDa). The best kinetic parameters of rHsEst were achieved using p-nitrophenyl valerate as substrate (KM = 78 µM, kcat = 0.67 s−1). rHsEst exhibited great stability to most metal ions tested and some solvents (diethyl ether, n-hexane, n-heptane). Purified rHsEst was effectively immobilized using Celite 545. Esterase activities of rHsEst were confirmed by substrate specificity studies. The presence of a serine residue in rHsEst active site was revealed through inhibition with PMSF. The pH for optimal activity of free rHsEst was 8, while for immobilized rHsEst, maximal activity was at a pH range between 8 to 10. Immobilization of rHsEst increased its thermostability, halophilicity and protection against inhibitors such as EDTA, BME and PMSF. Remarkably, immobilized rHsEst was stable and active in NaCl concentrations as high as 5M. These biochemical characteristics of immobilized rHsEst reveal its potential as a biocatalyst for industrial applications.
... Since their identification and reclassification four decades ago, the study of microorganisms from the Domain Archaea has proven to be a continuous source of exciting discoveries, contributing to the characterization of their unique molecular mechanisms, metabolisms, ecophysiology, phylogeny, and cell biology (Spang et al., 2017;Lyu et al., 2018;Baker et al., 2020;van Wolferen et al., 2022). These findings have revealed the impact that archaea play in nutrient cycles, biotechnology advancements, and One-Health microbiomes (Pfeifer et al., 2021;Hoegenauer et al., 2022). In addition, the advancements in archaeal biology have highlighted the key position that archaea occupy in the evolution and diversification of the Tree of Life (Spang et al., 2017;Baker et al., 2020). ...
... Surface layers have already shown potential for applications in biotechnology, medicine and environmental science, and an improved understanding of these structures could lead to further applications in fields as diverse as ultrafiltration membranes and biosensors (Pfeifer et al., 2021;Pfeifer et al., 2022;Douglas et al., 1986). These applications in the real world are a long way from the extreme environments in which archaea are often found. ...
The surface layer of Sulfolobus acidocaldarius consists of a flexible but stable outer protein layer that interacts with an inner, membrane-bound protein.
... Species from the genus Methanothermobacter, such as Methanothermobacter thermoautotrophicus and Methanothermobacter marburgensis, show good growth yields and shorter doubling times (of 2 h) than other thermophilic archaea (doubling times from less than an hour to several days) [68,69]. They also perform outstandingly in terms of MPRs in continuous stirred-tank reactors compared with other methanogens [70]. Methanothermobacter thermoautotrophicus can be cultivated, resulting in an MPR of 40 * with a 59% methane content, while for Methanothermobacter marburgensis an MPR of 288 * with a methane content of 96% was reported [71,72]. ...
... Species from the genus Methanothermobacter, such as Methanothermobacter thermoautotrophicus and Methanothermobacter marburgensis, show good growth yields and shorter doubling times (of 2 h) than other thermophilic archaea (doubling times from less than an hour to several days) [68,69]. They also perform outstandingly in terms of MPRs in continuous stirred-tank reactors compared with other methanogens [70]. ...
With the increasing use of renewable energy resources for the power grid, the need for long-term storage technologies, such as power-to-gas systems, is growing. Biomethanation provides the opportunity to store energy in the form of the natural gas-equivalent biomethane. This study investigates a novel plug flow reactor that employs a helical static mixer for the biological methanation of hydrogen and carbon dioxide. In tests, the reactor achieved an average methane production rate of 2.5 LCH4LR∗d (methane production [LCH4] per liter of reactor volume [LR] per day [d]) with a maximum methane content of 94%. It demonstrated good flexibilization properties, as repeated 12 h downtimes did not negatively impact the process. The genera Methanothermobacter and Methanobacterium were predominant during the initial phase, along with volatile organic acid-producing, hydrogenotrophic, and proteolytic bacteria. The average ratio of volatile organic acid to total inorganic carbon increased to 0.52 ± 0.04, while the pH remained stable at an average of pH 8.1 ± 0.25 from day 32 to 98, spanning stable and flexible operation modes. This study contributes to the development of efficient flexible biological methanation systems for sustainable energy storage and management.
... This requirement inhibits the contamination of other microorganisms in their culture media, so gives it an advantage in the utilization of halophilic archaea and their bioactive compounds in biotechnology. This restriction minimizes the risk of contamination during the cultivation process [52]. As previously mentioned, halophilic archaea produce pigment in shades of red; the major carotenoid is bacterioruberin [53]. ...
This study aimed to assess the efficacy of a bacterioruberin-rich carotenoid extract (HAE) derived from the halophilic archaea Halorubrum ezzemoulense DSM 19316 in protecting crude fish oil against thermal oxidation. The research used fish oil derived from anchovies, which had a peroxide value (PV) of 6.44 ± 0.81 meq O2 kg−1. To assess the impact of HAE on the thermal stability and post-oxidation characteristics of fish oil, several concentrations of HAE were added to the fish oil samples: 0 ppm (no additive) (HAE0), 50 ppm (HAE50), 100 ppm (HAE100), 500 ppm (HAE500), and 1000 ppm (HAE1000). Furthermore, a control group was established with the addition of 100 ppm butylated hydroxytoluene (BHT100) in order to evaluate the effectiveness of HAE with a synthetic antioxidant that is commercially available. Prior to the fast oxidation experiment, thermogravimetric analysis was conducted on samples from all experimental groups. At the conclusion of the examination, it was seen that the HAE500 and HAE1000 groups exhibited a delay in the degradation temperature. The experimental groups underwent oxidation at a temperature of 55.0 ± 0.5 °C for a duration of 96 h. The measurement of PV was conducted every 24 h during this time. PV in all experimental groups exhibited a time-dependent rise (p < 0.05). However, the HAE500 group had the lowest PV measurement at the conclusion of the 96 h period (p < 0.05). Significant disparities were detected in the fatty acid compositions of the experimental groups at the completion of the oxidation experiment. The HAE500 group exhibited the highest levels of EPA, DHA, and ΣPUFA at the end of oxidation, with statistical significance (p < 0.05). Through the examination of volatile component analysis, specifically an oxidation marker, it was shown that the HAE500 group exhibited the lowest level of volatile components (p < 0.05). Consequently, it was concluded that the addition of HAE to fish oil provided superior protection compared to BHT at an equivalent rate. Moreover, the group that used 500 ppm HAE demonstrated the highest level of performance in the investigation.
