Abstract
To obtain high-cell-density cultures of Schizochytrium sp. FJU-512 for DHA production, two stages of fermentation strategy were used and carbon/nitrogen ratio, DO and temperature were controlled at different levels. The final dry cell weight, total lipid production and DHA yield in 15 l bioreactor reached 103.9, 37.2 and 16.0 g/l, respectively. For the further study of microbial growth and DHA production dynamics, we established a set of kinetic models for the fed-batch production of DHA by Schizochytrium sp. FJU-512 in 15 and 100 l fermenters and a compensatory parameter n was integrated into the model in order to find the optimal mathematical equations. A modified Logistic model was proposed to fit the cell growth data and the following kinetic parameters were obtained: µm = 0.0525/h, Xm = 100 g/l and n = 4.1717 for the 15 l bioreactor, as well as µm = 0.0382/h, Xm = 107.4371 g/l and n = 10 for the 100 l bioreactor. The Luedeking–Piret equations were utilized to model DHA production, yielding values of α = 0.0648 g/g and β = 0.0014 g/g/h for the 15 l bioreactor, while the values of α and β obtained for the 100 l fermentation were 0.0209 g/g and 0.0030 g/g/h. The predicted results compared with experimental data showed that the established models had a good fitting precision and were able to exactly depict the dynamic features of the DHA production process.
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Abbreviations
- µ m :
-
Maximum specific growth rate (1/h)
- X :
-
Biomass concentration (g/l)
- X m :
-
Maximum biomass concentration (g/l)
- P :
-
DHA concentration (g/l)
- α :
-
Growth-associated product formation coefficient (g/g)
- β :
-
Non-growth-associated product formation coefficient (g/g/h)
References
Bhattacharya M, Guchhait S, Biswas D, Datta S (2015) Waste lubricating oil removal in a batch reactor by mixed bacterial consortium: a kinetic study. Bioprocess Biosyst Eng 38(11):2095–2106. https://doi.org/10.1007/s00449-015-1449-9
Chang G, Wu J, Jiang C, Tian G, Wu Q, Chang M, Wang X (2014) The relationship of oxygen uptake rate and k(L)a with rheological properties in high cell density cultivation of docosahexaenoic acid by Schizochytrium sp. S31. Bioresour Technol 152:234–240. https://doi.org/10.1016/j.biortech.2013.11.002
Chi ZY, Liu Y, Frear C, Chen SL (2009) Study of a two-stage growth of DHA-producing marine algae Schizochytrium limacinum SR21 with shifting dissolved oxygen level. Appl Microbiol Biotechnol 81(6):1141–1148. https://doi.org/10.1007/s00253-008-1740-7
Chodchoey K, Verduyn C (2012) Growth, fatty acid profile in major lipid classes and lipid fluidity of Aurantiochytrium Mangrovei Sk-02 as a function of growth temperature. Braz J Microbiol 43(1):187–200. https://doi.org/10.1590/S1517-838220120001000020
De Swaaf ME, Sijtsma L, Pronk JT (2003) High-cell-density fed-batch cultivation of the docosahexaenoic acid producing marine alga Crypthecodinium cohnii. Biotechnol Bioeng 81(6):666–672. https://doi.org/10.1002/bit.10513
Gaden EL (2000) Fermentation process kinetics (Reprinted from J of Biochemical and Microbiological Technology and Engineering, vol 1, pg 413, 1959). Biotechnol Bioeng 67(6):629–635. https://doi.org/10.1002/(sici)1097-0290(20000320)67:6<629::aid-bit2>3.0.co;2-p
Huang JZ, Aki T, Yokochi T, Nakahara T, Honda D, Kawamoto S, Shigeta S, Ono K, Suzuki O (2003) Grouping newly isolated docosahexaenoic acid-producing thraustochytrids based on their polyunsaturated fatty acid profiles and comparative analysis of 18S rRNA genes. Mar Biotechnol 5(5):450–457. https://doi.org/10.1007/s10126-002-0110-1
Kim YJ, Chung HY (2007) Antioxidative and anti-inflammatory actions of docosahexaenoic acid and eicosapentaenoic acid in renal epithelial cells and macrophages. J Med Food 10(2):225–231. https://doi.org/10.1089/jmf.2006.092
Lukiw WJ, Bazan NG (2008) Docosahexaenoic acid and the aging brain. J Nutr 138(12):2510–2514. https://doi.org/10.3945/jn.108.096016
Meadus WJ, Duff P, Rolland D, Aalhus JL, Uttaro B, Dugan MER (2011) Feeding docosahexaenoic acid to pigs reduces blood triglycerides and induces gene expression for fat oxidation. Can J Anim Sci 91(4):601–612. https://doi.org/10.4141/cjas2011-055
Metz JG, Roessler P, Facciotti D, Levering C, Dittrich F, Lassner M, Valentine R, Lardizabal K, Domergue F, Yamada A, Yazawa K, Knauf V, Browse J (2001) Production of polyunsaturated fatty acids by polyketide synthases in both prokaryotes and eukaryotes. Science 293(5528):290–293. https://doi.org/10.1126/science.1059593
Panda AK, Khan RH, Rao KB, Totey SM (1999) Kinetics of inclusion body production in batch and high cell density fed-batch culture of Escherichia coli expressing ovine growth hormone. J Biotechnol 75(2–3):161–172. https://doi.org/10.1016/s0168-1656(99)00157-1
Pasquet V, Ulmann L, Mimouni V, Guiheneuf F, Jacquette B, Morant-Manceau A, Tremblin G (2014) Fatty acids profile and temperature in the cultured marine diatom Odontella aurita. J Appl Phycol 26(6):2265–2271. https://doi.org/10.1007/s10811-014-0252-3
Qu L, Ji XJ, Ren LJ, Nie ZK, Feng Y, Wu WJ, Ouyang PK, Huang H (2011) Enhancement of docosahexaenoic acid production by Schizochytrium sp. using a two-stage oxygen supply control strategy based on oxygen transfer coefficient. Lett Appl Microbiol 52(1):22–27. https://doi.org/10.1111/j.1472-765X.2010.02960.x
Qu L, Ren L-J, Sun G-N, Ji X-J, Nie Z-K, Huang H (2013) Batch, fed-batch and repeated fed-batch fermentation processes of the marine thraustochytrid Schizochytrium sp for producing docosahexaenoic acid. Bioprocess Biosyst Eng 36(12):1905–1912. https://doi.org/10.1007/s00449-013-0966-7
Ratledge C (2004) Fatty acid biosynthesis in microorganisms being used for single cell oil production. Biochimie 86(11):807–815. https://doi.org/10.1016/j.biochi.2004.09.017
Ren LJ, Ji XJ, Huang H, Qu L, Feng Y, Tong QQ, Ouyang PK (2010) Development of a stepwise aeration control strategy for efficient docosahexaenoic acid production by Schizochytrium sp. Appl Microbiol Biotechnol 87(5):1649–1656. https://doi.org/10.1007/s00253-010-2639-7
Ren L-J, Sun L-N, Zhuang X-Y, Qu L, Ji X-J, Huang H (2014) Regulation of docosahexaenoic acid production by Schizochytrium sp.: effect of nitrogen addition. Bioprocess Biosyst Eng 37(5):865–872. https://doi.org/10.1007/s00449-013-1057-5
Song XJ, Zhang XC, Kuang CH, Zhu LY, Zhao XB (2010) Batch kinetics and modeling of DHA production by S. limacinum OUC88. Food Bioprod Process 88(C1):26–30. https://doi.org/10.1016/j.fbp.2009.12.004
Sun L, Ren L, Zhuang X, Ji X, Yan J, Huang H (2014) Differential effects of nutrient limitations on biochemical constituents and docosahexaenoic acid production of Schizochytrium sp. Bioresour Technol 159:199–206. https://doi.org/10.1016/j.biortech.2014.02.106
Surendhiran D, Vijay M, Sivaprakash B, Sirajunnisa A (2015) Kinetic modeling of microalgal growth and lipid synthesis for biodiesel production. 3 Biotech 5(5):663–669. https://doi.org/10.1007/s13205-014-0264-3
Suzuki T, Yamane T, Shimizu S (1986) Kinetics and effect of nitrogen source feeding on production of poly-β-hydroxybutyric acid by fed-batch culture. Appl Microbiol Biotechnol 24(5):366–369. https://doi.org/10.1007/bf00294591
Thyagarajan T, Puri M, Vongsvivut J, Barrow CJ (2014) Evaluation of bread crumbs as a potential carbon source for the growth of thraustochytrid species for oil and omega-3 production. Nutrients 6(5):2104–2114. https://doi.org/10.3390/nu6052104
Unagul P, Assantachai C, Phadungruengluij S, Suphantharika M, Verduyn C (2005) Properties of the docosahexaenoic acid-producer Schizochytrium mangrovei Sk-02: effects of glucose, temperature and salinity and their interaction. Bot Mar 48(5–6):387–394. https://doi.org/10.1515/bot.2005.052
Ward OP, Singh A (2005) Omega-3/6 fatty acids: alternative sources of production. Process Biochem 40(12):3627–3652. https://doi.org/10.1016/j.procbio.2005.02.020
Yamane Y, Higashida K, Nakashimada Y, Kakizono T, Nishio N (1997) Influence of oxygen and glucose on primary metabolism and astaxanthin production by Phaffia rhodozyma in batch and fed-batch cultures: kinetic and stoichiometric analysis. Appl Environ Microbiol 63(11):4471–4478
Yokochi T, Honda D, Higashihara T, Nakahara T (1998) Optimization of docosahexaenoic acid production by Schizochytrium limacinum SR21. Appl Microbiol Biotechnol 49(1):72–76. https://doi.org/10.1007/s002530051139
Zeng Y, Ji XJ, Lian M, Ren LJ, Jin LJ, Ouyang PK, Huang H (2011) Development of a temperature shift strategy for efficient docosahexaenoic acid production by a marine fungoid protist, Schizochytrium sp. HX-308. Appl Biochem Biotechnol 164(3):249–255. https://doi.org/10.1007/s12010-010-9131-9
Zhuo Z, Zhang L, Mu Q, Lou Y, Gong Z, Shi Y, Ouyang G, Zhang Y (2009) The effect of combination treatment with docosahexaenoic acid and 5-fluorouracil on the mRNA expression of apoptosis-related genes, including the novel gene BCL2L12, in gastric cancer cells. Vitro Cell Dev Biol Anim 45(1–2):69–74. https://doi.org/10.1007/s11626-008-9154-5
Acknowledgements
This work was financially supported by the National Natural Science Foundation of China (No. 21406130). We sincerely thank Professors Chun Men and Hang Wang (Fuzhou University, Fuzhou, Fujian 350108, PR China) for providing the MATLAB program.
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Zhang, M., Wu, W., Guo, X. et al. Mathematical modeling of fed-batch fermentation of Schizochytrium sp. FJU-512 growth and DHA production using a shift control strategy. 3 Biotech 8, 162 (2018). https://doi.org/10.1007/s13205-018-1187-1
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DOI: https://doi.org/10.1007/s13205-018-1187-1