Tailor-made solvents for microbial carotenoids recovery

**Background:** Microbial carotenoids (e.g., β-carotene, astaxanthin, lutein) are valuable natural pigments with antioxidant and antimicrobial properties, used in food, feed, cosmetics, and pharmaceuticals. They are produced intracellularly by yeasts, bacteria, and microalgae, requiring effective extraction methods. Traditional extraction relies on volatile organic compounds (VOCs) like hexane and acetone, which pose environmental and health risks. This review explores the potential of tailor-made solvents—ionic liquids (ILs) and deep eutectic solvents (DES)—as greener alternatives for microbial carotenoid recovery. It also discusses in silico tools (COSMO-RS/SAC) for predicting solvent performance and addresses challenges in carotenoid separation and solvent recycling.

**Methods:** The authors conducted a narrative review of literature from 2014–2023, supplemented by a bibliometric analysis of the Scopus database using search terms for carotenoids, microorganisms, eutectic solvents, and ionic liquids. They summarized key studies on IL and DES extraction of carotenoids from various microbial sources (e.g., Rhodotorula glutinis, Phaffia rhodozyma, Haematococcus pluvialis, Scenedesmus sp.). The review also covers COSMO-based computational models for predicting solute–solvent interactions via sigma-profiles and activity coefficients at infinite dilution (lnγi∞).

**Key Results:** The bibliometric analysis identified over 1,211 documents published from 2014–2023, with ~72% related to ILs and ~28% to DES. Publications increased from 5 (DES) and 31 (ILs) in 2015 to 114 (DES) and 196 (ILs) in 2023. India, China, and Brazil were the most prolific countries. In silico COSMO models showed that carotenes (e.g., β-carotene) have only non-polar regions, favoring non-polar solvents, while xanthophylls (e.g., astaxanthin) have additional polar regions, requiring solvents with both non-polar and some polar character. Longer alkyl chain carboxylic acids (used as HBD or anion precursors) increased non-polar character and lowered lnγi∞, indicating higher affinity for carotenoids. Experimental studies reported high extraction yields: e.g., 206.65 ± 10.75 μg/mL β-carotene from R. glutinis using [DEAPA][Hex] PIL; 97.2% astaxanthin recovery from H. pluvialis using ethanolammonium caproate (EAC) with microwave assistance; 47.9 ± 0.8% (w/w) astaxanthin and 46.0 ± 1.0% (w/w) β-carotene from P. rhodozyma using choline chloride:butyric acid DES. Separation of carotenoids from IL/DES extracts was achieved via liquid–liquid extraction, three-phase partitioning, antisolvent precipitation, or chromatography. Some studies proposed direct use of carotenoid-rich DES extracts in final formulations (e.g., biodegradable biofilms). Life Cycle Assessment (LCA) and techno-economic analysis (TEA) are rarely applied; one LCA study on IL-based fucoxanthin extraction reported that IL reuse reduced environmental impact by 8–14%.

**Clinical Implications:** Although this is a non-clinical review, the findings have indirect relevance to human health. Microbial carotenoids are potent antioxidants that may reduce risks of neural disorders, certain cancers, cardiovascular diseases, and cataracts. The development of greener, more efficient extraction methods using ILs and DES could facilitate the production of high-purity carotenoids for nutraceutical and pharmaceutical applications. However, the review emphasizes that biocompatibility, economic feasibility, and environmental impact of these solvents must be rigorously assessed before industrial adoption. The use of in silico tools can accelerate solvent selection and reduce resource waste.