Monascus purpureus was grown in submerged liquid culture using ammonium sulfate, sodium nitrate, and peptone as nitrogen sources while initial medium pH was adjusted to 2.5, 5.5, 6.5, or 8.0. The combined effect of culture pH and nitrogen source on the biosynthesis of yellow (ankaflavin and monascin) and orange (rubropunctatin and monascorubrin) pigments, plus the mycotoxin citrinin, was evaluated chromatographically. Optimum cultivation conditions, that is, initial pH 2.5 and 8.8 g/L peptone as a nitrogen source, resulted in high levels of production of yellow and orange pigments (sum of pigment concentration 1,138 mg/L) and negligible citrinin concentration (2 mg/L).

Department of Biotechnology University of Chemistry and Technology Prague 6 Czech Republic

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Bazin, I. , Faucet‐Marquis, V. , Monje, M. C. , El Khoury, M. , Marty, J. L. , & Pfohl‐Leszkowicz, A. (2013). Impact of pH on the stability and the cross‐reactivity of ochratoxin A and citrinin. Toxins, 5(12), 2324–2340. 10.3390/toxins5122324 PubMed DOI PMC

Carels, M. , & Shepherd, D. (1977). The effect of different nitrogen sources on pigment production and sporulation of Monascus species in submerged, shaken culture. Canadian Journal of Microbiology., 23(10), 1360–1372. 10.1139/m77-205 PubMed DOI

Chen, M. H. , & Johns, M. R. (1993). Effect of pH and nitrogen source on pigment production by Monascus purpureus . Applied Microbiology and Biotechnology, 40, 132–138.

Chen, M. H. , & Johns, M. R. (1994). Effect of carbon source on ethanol and pigment production by Monascus purpureus . Enzyme Microbiology Technology, 16, 584–590.

Chen, W. , Chen, R. , Liu, Q. , He, Y. , He, K. , Ding, X. , … Chen, F. (2017). Orange, red, yellow: Biosynthesis of azaphilone pigments in Monascus fungi. Chemical Science, 8(7), 4917–4925. 10.1039/c7sc00475c PubMed DOI PMC

Chen, W. , Feng, Y. , Molnár, I. , & Chen, F. (2019). Nature and nurture: Confluence of pathway determinism with metabolic and chemical serendipity diversifies Monascus azaphilone pigments. Natural Product Reports, 36, 561–572. 10.1039/C8NP00060C PubMed DOI PMC

Commission Regulation (EU) No 212/2014. Regulation (EC) No 1881/2006 as regards maximum levels of the contaminant citrinin in food supplements based on rice fermented with red yeast Monascus purpureus. Official Journal of the European Union. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32014R0212&from=EN.

EFSA Panel of Contaminants in the Food Chain (CONTAM) (2012). Scientific Opinion on the risks for public and animal health related to the presence of citrinin in food and feed. EFSA Journal, 10(3), 2605 10.2903/j.efsa.2012.2605 DOI

Feng, Y. , Shao, Y. , & Chen, F. (2012). Monascus pigments. Applied Microbiology and Biotechnology, 96, 1421–1440. 10.1007/s00253-012-4504-3 PubMed DOI

Föllmann, W. , Behm, C. , & Degen, G. H. (2014). Toxicity of the mycotoxin citrinin and its metabolite dihydrocitrinone and of mixtures of citrinin and ochratoxin A in vitro. Archives of Toxicology, 88(5), 1097–1107. 10.1007/s00204-014-1216-8 PubMed DOI

Hajjaj, H. , Klaebé, A. , Goma, G. , Blanc, P. J. , Barbier, E. , & Francois, J. (2000). Medium‐chain fatty acids affect citrinin production in the filamentous fungus Monascus ruber . Applied and Environmental Microbiology, 66, 1120–1125. 10.1128/AEM.66.3.1120-1125.2000 PubMed DOI PMC

He, Y. , & Cox, R. J. (2016). The molecular steps of citrinin biosynthesis in fungi. Chemical Science, 7, 2119–2127. 10.1039/c5sc04027b PubMed DOI PMC

Hirota, M. , Mehta, A. , Yoneyama, K. , & Kitabatake, N. (2002). A major decomposition product, citrinin H2, from citrinin on heating with moisture. Bioscience, Biotechnology, and Biochemistry, 66(1), 206–210. 10.1271/bbb.66.206 PubMed DOI

Huang, T. , Wang, M. , Shi, K. , Chen, G. , Tian, X. , & Wu, Z. (2017). Metabolism and secretion of yellow pigment under high glucose stress with Monascus ruber . AMB Express, 7, 79 10.1186/s13568-017-0382-5 PubMed DOI PMC

Kang, B. , Zhang, X. , Wu, Z. , Wang, Z. , & Park, S. (2014). Production of citrinin‐free Monascus pigments by submerged culture at low pH. Enzyme and Microbial Technology, 55, 50–57. 10.1016/j.enzmictec.2013.12.007 PubMed DOI

Lee, C. L. , Hung, Y. P. , Hsu, Y.‐W. , & Pan, T. M. (2013). Monascin and ankaflavin have more anti‐atherosclerosis effect and less side effect involving increasing creatinine phosphokinase activity than monacolin K under the same dosages. Journal of Agicultural and Food Chemistry, 61, 143–150. 10.1021/jf304346r PubMed DOI

Lee, C. L. , Lin, P. Y. , Hsu, Y. W. , & Pan, T. M. (2015). Monascus‐fermented monascin and ankaflavin improve the memory and learning ability in amyloid β‐protein intracerebroventricular‐infused rat via the suppression of Alzheimer's disease risk factors. Journal of Functional Foods, 18, 387–399. 10.1016/j.jff.2015.08.002 DOI

Lee, C. L. , Wen, J. A. , Hsu, Y. W. , & Pan, T. M. (2018). The blood lipid regulation of Monascus‐produced monascin and ankaflavin via the suppression of low‐density lipoprotein cholesterol assembly and stimulation of apolipoprotein A1 expression in the liver. Journal of Microbiology, Immunology and Infection, 51(1), 27–37. 10.1016/j.jmii.2016.06.003 PubMed DOI

Lv, J. , Qian, G. F. , Chen, L. , Liu, H. , Xu, H. X. , Xu, G. R. , … Zhang, C. (2018). Efficient biosynthesis of natural yellow pigments by Monascus purpureus in a novel integrated fermentation system. Journal of Agriculture and Food Chemistry, 66(4), 918–925. 10.1021/acs.jafc.7b05783 PubMed DOI

Pastrana, L. , Loret, M. O. , Blanc, P. J. , & Goma, G. (1996). Production of citrinin by Monascus ruber submerged culture in chemically defined media. Acta Biotechnologica, 16, 315–319. 10.1002/abio.370160414 DOI

Patakova, P. (2013). Monascus secondary metabolites: Production and biological activity. Journal of Industrial Microbiology & Biotechnology, 40(2), 169–181. 10.1007/s10295-012-1216-8 PubMed DOI

Patakova, P. , Branska, B. , & Patrovsky, M. (2016). Monascus secondary metabolites In Mérillon J. M. & Ramawat K. G. (Eds.), Fungal metabolites (Reference series in phytochemistry) (pp. 821–851). Heidelberg, Germany: Springer International Publishing.

Shi, K. , Song, D. , Chen, G. , Pistolozzi, M. , Wu, Z. , & Quan, L. (2015). Controlling composition and colour characteristics of Monascus pigments by pH and nitrogen sources in submerged fermentation. Journal of Bioscience and Bioengineering, 120, 145–154. 10.1016/j.jbiosc.2015.01.001 PubMed DOI

Wong, H. C. , Lin, Y. C. , & Koehler, P. E. (1981). Regulation of growth and pigmentation of Monascus purpureus by carbon and nitrogen concentrations. Mycologia, 73(4), 649–654. 10.2307/3759491 DOI

Yang, Y. , Liu, B. , Du, X. , Li, P. , Liang, B. , Cheng, X. , … Wang, S. (2015). Complete genome sequence and transcriptomics analyses reveal pigment biosynthesis and regulatory mechanisms in an industrial strain, Monascus purpureus YY‐1. Scientific Reports, 5, 8331 10.1038/srep08331 PubMed DOI PMC

Yongsmith, B. , Tabloka, W. , Yongmanitchai, W. , & Bavavoda, R. (1993). Culture conditions for yellow pigment formation by Monascus sp. KB 10 grown on cassava medium. World Journal of Microbiology and Biotechnology, 9(1), 85–100. 10.1007/BF00656524 PubMed DOI

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