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8(5)08

Nauka innov. 2012, 8(5):72–78
https://doi.org/10.15407/scin8.05.078

V.Yu. Yatsyshyn1, M. Kluz2, D.V. Fedorovych1, А.А. Sibirny1,2
1Institute of Cell Biology, NAS of Ukraine, Lviv
2Rzeszowski Uniwersytet, Poland

 

Construction of the Overproducers and Development of Technology for Flavin Mononucleotide Production Based on Yeast Candida famata

Section: Scientific and Technical Innovative Projects of National Academy of Sciences of Ukraine
Language: Ukrainian
Abstract: The strains of the yeast Candida famata containing 5-6 copies of FMN1 gene (encoding riboflavin kinase) were constructed. The optimal conditions for flavin mononucleotide (FMN) synthesis under batсh and feed-batсh cultivation were investigated. The medium components and cultivation conditions for maximal accumulation of product – FMN were optimized.
Key words: flavin mononucleotide (FMN), yeast, Candida famata, oversynthesis, overproducers.

References:
1. Rivlin R.S. Riboflavin. Present Knowledge in Nutrition. Ed by E.K. Ziegler and L.J. Filer, International Life Sciences Institut, 1996. P. 167-173.
2. Burgess C.M., Smid E.J., van Sinderen D. Bacterial vitamin B2, B11 and B12 overproduction: An overview. Intern. J. Food Microbiol. 2009. Vol. 133, No. 1–2. P. 1-7.
https://doi.org/10.1016/j.ijfoodmicro.2009.04.012
3. Abbas C.A., Sibirny A.A. Genetic control of biosynthesis and transport of riboflavin and flavin nucleotides and construction of robust biotechnological producers. Microbiol . Mol. Biol. Rev. 2011. Vol. 75, No. 2. P. 321-360.
https://doi.org/10.1128/MMBR.00030-10
4. Massey V. The chemical and biological versatility of riboflavin. Biochem. Soc. Trans. 2000. 28. P. 283-296.
https://doi.org/10.1042/bst0280283
5. DeColibus L., Mattevi A. New frontiers in structural flavoenzymology. Curr.Opin.Struct. Biol. 2006. Vol. 16, No. 4. P. 722-728.
https://doi.org/10.1016/j.sbi.2006.10.003
6. Jacishin V.Ju., Fedorovich D.V., Sibirnyj A.A. Mikrob nyj sintez flavinovyh nukleotidov (obzor). Prikl. biohim. mikrobiol. 2009. T. 45, No. 2. S. 133-142 [in Russian].
7. Powers H.J. Riboflavin (vitamin B2) and health. Amer. J. Clin. Nutr.  2003. Vol. 77, No. 6. P. 1352-1360.
8. Borzenko I.A. Kliniko-farmacevticheskie aspekty primenenija riboflavina i riboflavinovyh kofermentov. Vracheb. delo. 1983. T. 10, No. 1. S. 4-8 [in Russian].
9. Berezovskij V.M. Himija vitaminov. Moskva: Pishhevaja prom., 1973. 632 s. [in Russian].
10. Kroschwitz J.I., Howe-Grant M., Kirk R.E., Othmer D.F. Kirk-Othmer Encyclopedia of Chemical Technology: [in 27 volumes]. New York: J. Wiley, 1998. V. 25: Vitamins to zone refining. 1998. P. 74-83.
11. Hamidova M.H. Riboflavinmononukleotid v glaznoj praktike. Vestn. oftal'mologii. 1973. T. 1, No. 2. S. 41-42 [in Russian].
12. Sybirnyj A.A., Fedorovych D.V., Borec'kyj Ju.R., Voronovs'kyj A.Ja. Mikrobnyj syntez flaviniv. Kyi'v: Nauk. dumka, 2006. 191 s. [in Ukrainian].
13. Hagihara T., Fujio T., Aisaka K. Cloning of FAD synthetasegene from Corynebacterium ammoniagenes and its application to FAD and FMN production. Appl. Microbiol. Biotechnol. 1995. Vol. 42, No. 5. P. 724-729.
https://doi.org/10.1007/BF00171952
14. Pat. 5514574 US, C12N 009/12; C12N 009/02; C12P 021/06; C12P 019/30. Method of producing flavine nucleotides. K. Kitatsuji, S. Ishino, S. Teshiba, M. Arimoto – Filing date 25.07.1994; Publication date 07.05.1996.
15. Stahmann K.P., Revuelta J.L., Seulberger H. Three biotechnical processes using Ashbya gossypii, Candida fama ta, or Bacillus subtilis compete with chemical ribo flavin production. Appl. Microbiol. and Biotechnol. 2000. Vol. 53, No. 5. P. 509-516.
https://doi.org/10.1007/s002530051649
16. Ishhuk O.P., Jacyshyn V.Ju., Dmytruk K.V. ta in. Gennoinzhenerne konstrujuvannja shtamiv flavinogennyh drizhdzhiv Candida famata z vysokoju aktyvnistju ryboflavinkinazy. Ukr. biohim. zhurn. 2006. T. 78, No. 5. S. 63-69 [in Ukrainian].
17. Voronovs'kyj A.Ja., Dmytruk K.V., Ishhuk O.P. ta in. Pat. 87684 Ukrai'na, MPK C 12 P 25/00, C 12 N 15/00. Sposib otrymannja flavinmononukleotydu (5’-FMN); zajavnyk i vlasnyk Instytut biologii' klityny NAN Ukrai'ny. No. a200612203; zajavl. 20.11.2006; opubl. 10.08.2009, bjul. No. 15 [in Ukrainian].
18. Yatsyshyn V. Y., Ischuk O. P., Voronovsky A. Y. et al. Production of flavin mononucleotide by metabolically engineered yeast Candida famata . Metabol. Eng. 2009. Vol. 11, No. 3. P. 163-167.
https://doi.org/10.1016/j.ymben.2009.01.004
19. Yatsyshyn V.Y., Fedorovych D.V., Sibirny A.A. Medium optimization for production of flavin mononucleotide by the recombinant strain of the yeast Candida famata using statistical designs. Biochem. Eng. J. 2010. Vol. 49, No. 1. P. 52-60.
https://doi.org/10.1016/j.bej.2009.11.010
20. Sambrook J., Fritsh E.F., Maniatis T. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1989.
21. Voronovsky A.A., Abbas C.A., Fayura L.R., Kshanovska B.V. et all. Development of a transformation system for the flavinogenic yeast Candida famata. FEMS Yeast Research. 2002. Vol. 2, No. 3. P. 381-388.
22. Plackett R.L., Burman J.P. The design of optimum multifactorial experiments . Biometrika. 1946. Vol. 33, No. 4. P. 305-325.
https://doi.org/10.1093/biomet/33.4.305
23. Montgomery D. C. Design and Analysis of Experiments. [4-th edn.]. New York: Wiley, 1997. 196 P.
24. Pat. 42499 Ukrai'na, MPK C 12 N 1/19. Shtam drizhdzhiv Candida famata IMV U-5028 – producent flavinmononukleotydu (5′-FMN). A.A. Sybirnyj, V.Ju. Jacyshyn, D.V. Fedorovych, O.P. Ishhuk, A.Ja. Voronovs'kyj; zajavnyk i vlasnyk Instytut biologii' klityny NAN Ukrai'ny. No. u 2009 00725; zajavl. 02.02.2009; opubl. 10.07.2009, bjul. No. 13 [in Ukrainian].
25. Strugovshhykova L.P., Fedorovych I.P., Shavlovs'kyj G.M. Vyjavlennja i dejaki vlastyvosti fosfataz Pichia guillie rmondi, jaki gidrolizujut' flavinmononukleotyd . Ukr. biohim. zhurn. 1973. T. 45, No. 2. S. 198-203 [in Ukrainian].