Enhancement of tacrolimus productivity in Streptomyces tsukubaensis by the use of novel precursors for biosynthesis |
| |
| Affiliation: | 1. Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, 34000 Kragujevac, Serbia;2. Centre for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia;3. Public Health Institute, Vranje, Serbia;4. Public Health Institute, Kragujevac, Serbia;1. Istituto di Psicopatologia, Roma, Italy;2. Department of Psychiatry, University Hospital Case Medical Center, Case Western Reserve University, Cleveland, Ohio, USA;1. Sleep Research Laboratory, University Health Network, Toronto Rehabilitation Institute, 550 University Avenue, Toronto, ON M5G 2A2, Canada;2. Department of Pulmonary Physiology & Sleep Medicine, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA 6009, Australia;3. Faculty of Science, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia;4. West Australian Sleep Disorders Research Institute, QEII Medical Centre, Hospital Avenue, Nedlands, WA 6009, Australia;5. Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College St, Toronto, ON M5S 3G9, Canada;6. Centre for Sleep Medicine and Circadian Biology, University of Toronto, 27 King’s College Cir, Toronto, ON M5S, Canada;7. Department of Medicine, University Health Network, Toronto General Hospital, 585 University Ave, Toronto, ON M5G 2N2, Canada;1. DECHEMA-Forschungsinstitut, Biochemical Engineering, Theodor-Heuss-Allee 25, 60486 Frankfurt am Main, Germany;2. Bielefeld University, Chair of Fermentation Engineering, Universitaetsstrasse 25, 33615 Bielefeld, Germany;3. Surflay Nanotec GmbH, Max-Planck-Str. 3, 12489 Berlin, Germany;4. W42 Industrial Biotechnology GmbH, Otto-Hahn-Straße 15, 44227 Dortmund, Germany |
| |
| Abstract: | In this report the optimization of biosynthesis of tacrolimus, the immunosupressant widely used in transplantology and dermatology was described. The enhancement of the productivity of Streptomyces tsukubaensis strain was achieved by development of new precursors of tacrolimus biosynthesis, which should allow to reduce the costs of the process.The enrichment of the fermentation medium in pyridine-2-carboxylic acid (picolinic acid), piperidine-2-carboxylic acid (pipecolic acid), pyridine-3-carboxylic acid (nicotinic acid) or pyridine-3-carboxylic acid amide (nicotinamide) caused significant growth of the productivity of tacrolimus: 7-fold, 6-fold, 3-fold and 5-fold, respectively. The optimum concentration of the precursors in medium was 0.0025–0.005%. The investigation of the kinetics of tacrolimus biosynthesis together with the analysis of the impact of tested compounds on the culture growth and NAD (nicotinamide adenine dinucleotide) concentration in S. tsukubaensis cells enables to put forward a hypothesis concerning the mechanism of action of tested culture medium additives. The compounds active as tacrolimus precursors (pipecolic and picolinic acids) are more effective than these active mainly as the growth promoters (nicotinamide and nicotinic acid). Nicotinamide and nicotinic acid – vitamin B3 components – promote S. tsukubaensis growth most probably due to the stimulation of NAD/NADP biosynthesis. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
