Optimization of Nutrients for Dinactin Production by a Marine Streptomyces sp. from the High Latitude Arctic

다국어 초록 (Multilingual Abstract)

Streptomyces sp. R-527F, which produces the macrotetrolide antibiotic dinactin, was isolated from the sediments of the Arctic Ocean. In this work, optimization of the nutrients required for dinactin production including medium development and precursor stimulation, were investigated. Optimization of the medium and replacement of polar sea water were achieved using a one factor at a time experiment in conjunction with statistical analysis using methods covering Plackett–Burman design, the steepest descent method and central composite design.
Dinactin production in the optimized medium was 160.8 mg/L, which was 47 fold higher than the control.
Supplementation of the fermentation with exogenous acetate (1.5 mmol/L), succinate (6 mmol/L), malonate (24 mmol/L) and citrate (6 mmol/L) further enhanced dinactin biosynthesis by 42.7, 122.3, 66.7, and 62.1%, respectively. The precursors, in particular succinate, facilitated sugar use and also increased pH levels. Furthermore, a six-pulse feeding of total 6 mmol/L succinate in a 5 L bioreactor fermentation yielded a maximal production of 279.0 mg/L dinactin, 124.1% higher than that without precursor stimulation.
This nutritional regulation process is easy to scale up and holds the potential for adaptation to industrial use.
Keywords: arctic actinomycete, fermentation, dinactin

참고문헌 (Reference)

1 Coutable, L, "Total synthesis of a novel macrotetrolide" 64 : 11296-11303, 2008

2 Dobler, M, "The crystal structure of nonactin" 55 : 1371-1384, 1972

3 Ivanova, V, "Structural elucidation of a bioactive metabolites production by Streptomyces avidinii SB9 strain, isolated from permafrost soil in Spitsbergen, Arctic" 24 : 2092-2095, 2010

4 Silva, L. J, "Streptomyces araujoniae produces a multiantibiotic complex with ionophoric properties to control Botrytis cinerea" 104 : 1298-1305, 2014

5 Cai, M, "Statistical optimization of medium composition for aspergiolide A production by marine-derived fungus Aspergillus glaucus" 36 : 381-389, 2009

6 Zeng, Y, "Polar microorganisms, a potential source for new natural medicines" 5 : 695-700, 2008

7 ezanka, T, "Pilot-plant cultivation of Streptomyces griseus producing homologues of nonactin by precursor-directed biosynthesis and their identification by LC/MS-ESI" 63 : 524-529, 2010

8 Ashworth, D. M, "On the biosynthetic origins of the hydrogen atoms in the macrotetrolide antibiotics: And their mode of assembly catalysed by a nonactin polyketide synthase" 1 : 1461-1467, 1989

9 Masurekar, P. S, "Nutritional and engineering aspects of microbial process development" 65 : 292-328, 2008

10 Zhou, W, "Nutrition and bioprocess development for efficient biosynthesis of an antitumor compound from marinederived fungus" 40 : 1131-1142, 2013

11 Nelson, M. E, "Nonactin biosynthesis:The initial committed step is the condensation of acetate (malonate)and succinate" 124 : 2894-2902, 2002

12 Al-Zereini, W, "New aromatic nitro compounds from Salegentibacter sp. T436, an Arctic Sea ice bacterium: Taxonomy, fermentation, isolation and biological activities" 60 : 301-308, 2007

13 Nelson, D. L, "Lehningers principles of biochemistry" Worth Publishers 2003

14 Janek, T, "Isolation and characterization of two new lipopeptide biosurfactants produced by Pseudomonas fluorescens BD5 isolated from water from the Arctic Archipelago of Svalbard" 101 : 6118-6123, 2010

15 Moller, C, "Intraspecific genetic diversity of Chaunopycnis alba detected by random amplified polymorphic DNA assay" 99 : 681-688, 1995

16 Umland, S. P, "Effects of cyclosporin A and dinactin on T-cell proliferation, interleukin-5 production, and murine pulmonary inflammation" 20 : 481-492, 1999

17 Osterhage, C, "Differences between marine and terrestrial Phoma species as determined by HPLC-D AD and HPLC-MS" 11 : 288-294, 2000

18 Ling, X, "Design and function on database of microorganisms from polar environments" 21 : 69-75, 2009

19 Li, L, "Cytotoxic metabolites from the antarctic psychrophilic fungus Oidiodendron truncatum" 75 : 920-927, 2012

20 Hansbro, P. M, "Cytokine/anti-cytokine therapy-novel treatments for asthma?" 163 : 81-95, 2011

21 Ringo, E, "Characterization of Carnobacterium divergens strain 6251 isolated from intestine of Arctic charr (Salvelinus alpinus L.)" 25 : 120-129, 2002

22 Kwon, H, "C-O bond formation by polyketide synthases" 297 : 1327-1330, 2002

23 Bernan, V. S, "Bioxalomycins new antibiotics produced by the marine Streptomyces sp. LL-31F508:Taxonomy and fermentation" 47 : 1417-1424, 1994

24 Zizka Z, "Biological effects of macrotetrolide antibiotics and nonactic acids" 43 : 7-14, 1998

25 Berdy, J, "Bioactive microbial metabolites" 58 : 1-26, 2005

26 Li, Y, "Bioactive asterric acid derivatives from the Antarctic ascomycete fungus Geomyces sp" 71 : 1643-1646, 2008

27 Huang, J.P, "Antimicrobial activity of PVP from an Antarctic bacterium, Janthinobacterium sp. Ant5-2, on multi-drugand methicillin resistant Staphylococcus aureus" 2 : 104-110, 2012

28 Niu, D, "A study on the insecticidal activity of Antarctic epiphyte Gliocladium catenulatum T31" 19 : 131-138, 2007

29 Abe, I, "A plant type III polyketide synthase that produces pentaketide chromone" 127 : 1362-1363, 2005