Effect of Gene SFU1 on Riboflavin Synthesis in Flavinogenic Yeast Candida famata

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ct of Gene SFU1 on Riboflavin Synthesis in Flavinogenic Yeast Candida famata Y. Petrovskaa, O. Lyzakb, K. Dmytruka, and A. Sibirnya, c, * a

Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, 79005 Ukraine bMax Planck Institute of Biochemistry, Martinsried, 82152 Germany c University of Rzeszow, Rzeszow, 35-601 Poland *e-mail: [email protected] Received March 10, 2020; revised March 24, 2020; accepted September 18, 2020

Abstract—Riboflavin or vitamin B2 is a necessary component for all living organisms since it is the precursor of flavin coenzymes FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide), which are involved in numerous enzymatic reactions. Flavinogenic yeast Candida famata overproduces riboflavin under iron starvation; however, regulation of this process is poorly understood. Regulatory gene SEF1 encoding the transcription activator has been identified. Its deletion blocks yeast’s ability to overproduce riboflavin under iron starvation. It is known that, in the pathogenic flavinogenic yeast C. albicans, Sfu1 (GATA-type transcription factor) represses SEF1. It is demonstrated in this study that deletion of the SEF1 gene in wild type C. famata leads to overproduction of riboflavin. Keywords: riboflavin, Candida famata, SFU1, yeast DOI: 10.3103/S0095452720050060

INTRODUCTION Riboflavin is an important component of any living organism since it is a metabolic precursor of the flavin nucleotides FMN and FAD, which act as coenzymes in numerous enzymatic reactions, most often oxidative metabolism reactions. Unlike plants, fungi, and most prokaryotes, animals are not able to synthesize riboflavin [1, 2]. An important prerequisite for the normal growth of animals and birds is a sufficient enrichment of feed with vitamin B2. Deficiency of riboflavin in feed rations leads to impairment of metabolism, growth retardation, deterioration of assimilation of amino acids and fats, amblyopia, dermatoses, and decrease in productivity and use of nutrients in forages. The introduction of riboflavin into the composition of premixes, feeds, and feed mixtures for animals and poultry increases their growth, improves the survival of young animals, increases productivity, and reduces feed costs per unit of product [3]. Therefore, the development of riboflavin production at the industrial level is extremely important. Riboflavin can be obtained by both chemical and microbial synthesis. The advantages of microbial synthesis include reduced waste, lower energy costs, and the use of renewable resources, such as sugars and vegetable oils [2, 4, 5]. In 2012, the total global production of riboflavin was approximately 9000 t, most of which was produced by BASF, DSM, and Hubei Guangji Pharmaceutical. Approximately 70% of these raw

materials are used in agriculture as feed additives, while the other 30% are used in the food industry and for clinical purposes. The global riboflavin market is estimated at from 200 to 230 million dollars per year depending on the price of riboflavin, which significan