Enhanced Large-Scale Production of Hahella chejuensis-Derived Prodigiosin and Evaluation of Its Bioactivity
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Prodigiosin as a high-valued compound, which is a microbial secondary metabolite, has the potential for antioxidant and anticancer effects. However, the large-scale production of functionally active Hahella chejuensis-derived prodigiosin by fermentation in a cost-effective manner has yet to be achieved. In the present study, we established carbon source-optimized medium conditions, as well as a procedure for producing prodigiosin by fermentation by culturing H. chejuensis using 10 L and 200 L bioreactors. Our results showed that prodigiosin productivity using 250 ml flasks was higher in the presence of glucose than other carbon sources, including mannose, sucrose, galactose, and fructose, and could be scaled up to 10 L and 200 L batches. Productivity in the glucose (2.5 g/l) culture while maintaining the medium at pH 6.89 during 10 days of cultivation in the 200 L bioreactor was measured and increased more than productivity in the basal culture medium in the absence of glucose. Prodigiosin production from 10 L and 200 L fermentation cultures of H. chejuensis was confirmed by high-performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometry (LC–MS) analyses for more accurate identification. Finally, the anticancer activity of crude extracted prodigiosin against human cancerous leukemia THP-1 cells was evaluated and confirmed at various concentrations. Conclusively, we demonstrate that culture conditions for H. chejuensis using a bioreactor with various parameters and ethanol-based extraction procedures were optimized to mass-produce the marine bacterium-derived high purity prodigiosin associated with anti-cancer activity.
Abstract
Prodigiosin as a high-valued compound, which is a microbial secondary metabolite, has the potential for antioxidant and anticancer effects. However, the large-scale production of functionally active Hahella chejuensis-derived prodigiosin by fermentation in a cost-effective manner has yet to be achieved. In the present study, we established carbon source-optimized medium conditions, as well as a procedure for producing prodigiosin by fermentation by culturing H. chejuensis using 10 L and 200 L bioreactors. Our results showed that prodigiosin productivity using 250 ml flasks was higher in the presence of glucose than other carbon sources, including mannose, sucrose, galactose, and fructose, and could be scaled up to 10 L and 200 L batches. Productivity in the glucose (2.5 g/l) culture while maintaining the medium at pH 6.89 during 10 days of cultivation in the 200 L bioreactor was measured and increased more than productivity in the basal culture medium in the absence of glucose. Prodigiosin production from 10 L and 200 L fermentation cultures of H. chejuensis was confirmed by high-performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometry (LC–MS) analyses for more accurate identification. Finally, the anticancer activity of crude extracted prodigiosin against human cancerous leukemia THP-1 cells was evaluated and confirmed at various concentrations. Conclusively, we demonstrate that culture conditions for H. chejuensis using a bioreactor with various parameters and ethanol-based extraction procedures were optimized to mass-produce the marine bacterium-derived high purity prodigiosin associated with anti-cancer activity.
참고문헌 (27)
- Wang SL, "Production and potential applications of bioconversion of chitin and protein-containing fishery byproducts into prodigiosin : a review", Molecules, 25, pp.2744~ (2020)
- 김성진, "Statistical Optimization of Medium Components for the Production of Prodigiosin by Hahella chejuensis KCTC 2396", Journal of Microbiology and Biotechnology, 18(12), pp.1903~1907 (2008), 한국미생물·생명공학회
- Williamson NR, "Biosynthesis of the red antibiotic, prodigiosin, in Serratia : identification of a novel 2-methyl-3-n-amyl-pyrrole(MAP)assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces", Mol. Microbiol, 56, pp.971~989 (2005)
- Harris AKP, "The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species-and strain-dependent genome context variation", Microbiology(Reading), 150, pp.3547~3560 (2004)
- Darshan N, "Prodigiosin and its potential applications", J. Food Sci. Technol, 52, pp.5393~5407 (2015)
- Perez-Tomas R, "New insights on the antitumoral properties of prodiginines", Curr. Med. Chem, 17, pp.2222~2231 (2010)
- Lee Jieun, "Effects of Hahella chejuensis-Derived Prodigiosin on UV-Induced ROS Production, Inflammation and Cytotoxicity in HaCaT Human Skin Keratinocytes", Journal of Microbiology and Biotechnology, 31(3), pp.475~482 (2021), 한국미생물·생명공학회[DOI]
- Nguyen TH, "Bioprocessing of marine chitinous wastes for the production of bioactive prodigiosin", Molecules, 26, pp.3138~ (2021)
- Yip CH, "Recent advancements in high-level synthesis of the promising clinical drug, prodigiosin", Appl. Microbiol. Biotechnol, 103, pp.1667~1680 (2019)
- Wei YH, "Enhanced production of prodigiosin-like pigment from Serratia marcescens SMdeltaR by medium improvement and oil-supplementation strategies", J. Biosci. Bioeng, 99, pp.616~622 (2005)
- Nguyen VB, "Utilization of crab waste for cost-effective bioproduction of prodigiosin", Mar. Drugs, 18, pp.523~ (2020)
- Rjazantseva IN, "Effect of various growth conditions on pigmentation of Serratia marcescens", Microbios, 79, pp.155~161 (1994)
- Andreeva IN, "The effect of the cultivation conditions on the growth and pigmentation of Serratia marcescens", Zh. Mikrobiol. Epidemiol. Immunobiol, 1999, pp.16~20 (1999)
- Han R, "High-level production of microbial prodigiosin : a review", J. Basic Microbiol, 61, pp.506~523 (2021)
- Nguyen VB, "Microbial reclamation of chitin and protein-containing marine by-products for the production of prodigiosin and the evaluation of its bioactivities", Polymers (Basel), 12, pp.1328~ (2020)
- Tao J-l, "Strategy for the improvement of prodigiosin production by a Serratia marcescens mutant through fed-batch fermentation", World J. Microbiol. Biotechnol, 21, pp.969~972 (2005)
- Mohammed. SJ, "A kinetic model for prodigiosin production by Serratia marcescens as a bio-colorant in bioreactor", AIP Conference Proceedings, 2213, pp.020027~ (2020)
- Chávez-Castilla. LR, "An integrated process for the in situ recovery of prodigiosin using micellar ATPS from a culture of Serratia marcescens", J. Chem. Technol. Biotechnol, 91, pp.2896~2903 (2016)
- Venil CK, "Optimization of culture conditions for flexirubin production by Chryseobacterium artocarpi CECT 8497 using response surface methodology", Acta Biochim. Pol, 62, pp.185~190 (2015)
- Lapenda JCL, "Cytotoxic effect of prodigiosin, natural red pigment, isolated from Serratia marcescens UFPEDA 398", Indian J. Microbiol, 60, pp.182~195 (2020)
- Yip CH, "Prodigiosin inhibits bacterial growth and virulence factors as a potential physiological response to interspecies competition", PLoS One, 16, pp.e0253445~ (2021)
- Hu W, "Evaluating the biological potential of prodigiosin from Serratia marcescens KH-001 against Asian citrus psyllid", J. Econ. Entomol, 114, pp.1219~1225 (2021)
- Stankovic N, "Properties and applications of undecylprodigiosin and other bacterial prodigiosins", Appl. Microbiol. Biotechnol, 98, pp.3841~3858 (2014)
- Ravindran A, "Molecular dynamics of the membrane interaction and localisation of prodigiosin", J. Mol. Graph. Model, 98, pp.107614~ (2020)
- Priya KA, "Microbiological Research In Agroecosystem Management", pp.11~12 (2013)
- Lee MS, "Bcl-2 regulates the onset of shiga toxin 1-induced apoptosis in THP-1 cells", Infect. Immun, 77, pp.5233~5244 (2009)
- Lee MS, "Shiga toxins : intracellular trafficking to the ER leading to activation of host cell stress responses", Toxins(Basel), 2, pp.1515~1535 (2010)