Production of economic and sustainable uniformly 13C labeled docosahexaenoic acid from heterotrophic marine protists Aurantiochytrium mangrovei and Crypthecodinium cohnii for medical applications, Mayssa Hachem

Mayssa Hachem
Department of Chemistry and Food Security and Technology Center, Khalifa University of Sciences and Technology
Abu Dhabi, 127788
United Arab Emirates

Abstract: Docosahexaenoic acid (DHA, 22:6n-3), an essential omega-3 long-chain polyunsaturated fatty acid (LC-PUFA), is primarily found in human’s brain and eyes, where it plays key roles in neuroprotection and offers various nutraceutical benefits (Hachem et al., 2020). In the context of prevention and potential treatment of neurodegenerative disease, particularly AD, researchers are investigating the way different forms of DHA, such as non-esterified DHA and DHA esterified in phospholipids (PL) and triglycerides (TG), influence the brain’s bioavailability (Hachem et al., 2016). For this purpose, labeled molecules (stable or radioactive isotopes) were used in in vitro, in vivo, and ex vivo studies to follow the DHA’s metabolism and conversion in the body. Several techniques have already been developed in order to examine the natural variations in 13C/12C ratio and trace n-3 PUFA metabolism (Metherel et al., 2019). However, tracing these metabolites can be challenging when the 13C/12C signatures of different compounds are too similar. In such cases, uniformly labeled 13C-DHA offers a powerful tool for precise analysis of DHA distribution, metabolism, and conversion into other metabolites. Unlike radioactive tracers, stable isotope applications like 13C-DHA pose no safety risks, making them ideal for human metabolism studies. The availability of sufficient amounts of uniformly labeled 13C-DHA is critical for studying its metabolic fate. Unfortunately, 13C-DHA is prohibitively expensive and often unavailable, with costs exceeding $2,000 for just 5 mg. To advance research, it is essential to develop cost-effective methods for producing 13C-DHA in various natural lipid forms, for use in both clinical nutrition studies and biological research. This situation stresses the need for alternative, cost-effective methods to study DHA metabolism, particularly its accumulation in the brain. One promising approach is to produce 13C-labeled LC-PUFA using microorganisms in photobioreactors or fermenters supplied with 13C-CO2 or 13C-glucose. This study has been conducted using Aurantiochytrium mangrovei cultured on a medium designed specifically for 13C lipid enrichment. This medium contained only uniformly labeled 13C glucose as the carbon source, while other nutrients like nitrogen were provided in inorganic forms to prevent dilution from organic compounds. A characteristic of A. mangrovei is its ability to produce DHA. This innovation aims to develop an economical and sustainable method for producing uniformly labeled 13C-DHA through the cultivation of heterotrophic protist A. mangrovei.
References:

1. Hachem, M.; Géloën, A.; Van, A. L.; Foumaux, B.; Fenart, L.; Gosselet, F.; Da Silva, P.; Breton, G.; Lagarde, M.; Picq, M.; Bernoud-Hubac, N., Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid. Molecular neurobiology 2016, 53 (5), 3205-3215.
2. Hachem, M.; Nacir, H.; Picq, M.; Belkouch, M.; Bernoud-Hubac, N.; Windust, A.; Meiller, L.; Sauvinet, V.; Feugier, N.; Lambert-Porcheron, S.; Laville, M.; Lagarde, M., Docosahexaenoic Acid (DHA) Bioavailability in Humans after Oral Intake of DHA-Containing Triacylglycerol or the Structured Phospholipid AceDoPC(®). Nutrients 2020, 12 (1).
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