Introduction of the yeast strain Cryptococcus uzbekistanensis as a melatonin producer: Evaluation of the effect of different growth media on melatonin production

Ali Nosrati


Melatonin (N-Acetyl-5-Methoxytryptamine) is a neuro-hormone produced in the pineal gland. It is found in animals, plants and fungi. Its biological properties contribute to the circadian rhythm, reproductive physiology and antioxidant activity. Melatonin is known to help reduce the effects of the jet lag by cultivating the necessary re-set of the body's circadian rhythm. Natural production of melatonin in humans depends on the amount of light as well as age; in fact, natural melatonin production declines with age. The present study was conducted to evaluate melatonin expression in yeast species. One hundred and thirty yeast species were screened and analyzed for melatonin production. It was found that Cryptococcus uzbekistanensis produced 46 ppm of melatonin in the optimized condition. The Box-Behnken methodology was used to identify significant factors in terms of the carbon source, temperature, growth incubation, and tryptophan concentration for optimization of melatonin production. The Response Surface Methodology (RSM) was applied to optimize the levels of these factors. In the presence of 3 ppm of tryptophan in the growth media, a growth incubation time of 72 hours, glucose as carbohydrate, and a temperature of 308 Kelvin, Cryptococcus uzbekistanensis produced the maximum concentration of melatonin. This is among few instances that a microorganism is found to produce melatonin and thus the results can be utilized for industrial production of melatonin.

Full Text:



Fauteck JD, Schmidt H, Lerchl A, Kurlemann G, Wittkowski W. Melatonin in epilepsy: first results of replacement therapy and first clinical results. Biologic Signals Recept 1999 Jan-Apr;8(1-2):105-101.

Hardeland R. Melatonin in aging and disease -multiple consequences of reduced secretion, options and limits of treatment. Aging Dis. 2012 Apr;3(2):194-225.

Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cochrane Database Syst Rev. 2001;(1):CD001520.

Acuña-Castroviejo D, Escames G, Figueira JC, de la Oliva P, Borobia AM, Acuña-Fernández C. Clinical trial to test the efficacy of melatonin in COVID-19. J Pineal Res 2020;00: e12683.

Rodriguez-Naranjo, M. I., Torija, M. J., Mas, A., Cantos-Villar, E., and GarciaParrilla, M. D. C (2012). Production of melatonin by Saccharomyces strains under growth and fermentation conditions. J. Pineal Res 53, 219–224. doi: 10.1111/j.1600-079X.2012. 00990.x

Fernandez-Cruz, E., González, B., Muñiz-Calvo, S. et al. Intracellular biosynthesis of melatonin and other indolic compounds in Saccharomyces and non-Saccharomyces wine yeasts. Eur Food Res Technol 245, 1553–1560 (2019).

Parra, Mª Ángeles & Gonzalez, Beatriz & Beltran, Gemma & Mas, Albert & Torija, Maria. (2019). Melatonin and glycolytic protein interactions are related to yeast fermentative capacity. Food Microbiol 87. 103398. 10.1016/

Minitab 17 Statistical Software (2010). [Computer software]. State College, PA: Minitab, Inc. (

D. C. Montgomery, John Wiley & Sons, New York, NY, USA, 1991.

Pandi-Perumal, S. R., Trakht, I., Srinivasan, V., Spence, D. W., Maestroni, G. J., Zisapel, N., &Cardinali, D.P. (2008). Physiological effects of melatonin: role of melatonin receptors and signal Transduction pathways. Progr Neurobiol 85(3):335-353.

Polimeni, G., Esposito, E., Bevelacqua, V., Guarneri, C., & Cuzzocrea, S. (2014). Role of Melatonin supplementation in neurodegenerative disorders. Front Biosci (Landmark Ed), 19, 429-446.

Rivara, S., Pala, D., Bedini, A., & Spadoni, G. (2015). Therapeutic uses of melatonin and Melatonin derivatives: a patent review (2012-2014). Expert Opin Ther Pat 25(4), 425-441.

El Moneim, N. A. A., El Masry, H., Sorial, M. M., Hewala, T. I., Embaby, A., & Sheweita, S. A Molecular Case-Control Study on the Association of Melatonin Hormone and rs#10830963 Single Nucleotide Polymorphism in its Receptor MTNR1B Gene with Breast Cancer. Middle East J Cancer 2015;6(1), 11-20.

Hill SM, Belancio VP, Dauchy RT, Xiang S, Brimer S, Mao L, Hauch A, Lundberg PW, Summers W, Yuan L, Frasch T, Blask DE. Melatonin: an inhibitor of breast cancer. Endocr Relat Cancer. 2015 Jun;22(3):R183-204.

Hevia, D., González‐Menéndez, P., Quiros‐González, I., Miar, A., Rodríguez‐García, A., Tan, D.X., & Sainz, R. M. Melatonin uptake through glucose transporters: a new target for melatonin inhibition of cancer. J Pineal Res 2015;58(2), 234-250. Rivendell News the Netherlands. [Online] Available at: pageid=276 [Accessed 29 Oct. 2015].

Public Assessment Report of the Medicines Evaluation Board in the Netherlands Melatonin TioFarma 1 mg, 3 mg and 5 mg tablets TioFarma b.v., the Netherlands Melatonin. 29 June 2012.

Mackey, M. Sleepless in America: A $32.4 Billion Business. [Online] The Fiscal Times. Available at: [Accessed 29 Oct. 2015].

Laforce, R., Rigozzi, K., Paganetti, M., Mossi, W., Guainazzi, P., & Calderari, G. Aspects of melatonin manufacturing and requirements for a reliable active component. Neurosignals 1999;8(1-2):143-146.



Best Quality Medical Supplies is a registered company in Untied States specializing in sales of medical equipment and supplies. We are a distributor for hospitals, doctor offices, medical clinics, nursing schools, and nursing homes within the United States. We also provide services for overseas clients. Click here for details and orders .

The most affordable web hosting service. Click here for details and orders.