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Optimization of the mated fermentation process for the production of lycopene by Blakeslea trispora NRRL 2895 (+) and NRRL 2896 (−)

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Abstract

The mated fermentation process for the production of lycopene by Blakeslea trispora NRRL 2895 (+) and NRRL 2896 (−) was systematically optimized in shake flasks. The ratio of the (+) to (−) strains, the lycopene cyclase inhibitors piperidine and creatinine, the trisporic acid structural analog abscisic acid, the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) precursor leucine, and the mevalonate kinase enhancer penicillin were all identified as key factors affecting lycopene biosynthesis. With an optimal ratio of 5:1 for the (+) to (−) strains and the addition of 6 g/L creatinine on day 3, the highest lycopene production was 98.1 ± 15.5 mg/L. Based on the above result, the addition of 0.1 g/L penicillin on day 4, 150 μmol/L abscisic acid on day 3 or 0.5 g/L leucine on day 4 enhanced lycopene production to 119.7 ± 17.2, 120.6 ± 12.3 and 135.2 ± 7.0 mg/L, respectively. Finally, an integrated strategy by combining the above key factors was developed, and the highest lycopene production of 156.2 ± 15.4 mg/L was obtained, which was enhanced by 134.9% comparing with its production of 66.5 ± 3.6 mg/L before the optimization process of this work. The results obtained in this study may be useful for large-scale industrial lycopene production.

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References

  1. Salman H, Bergman M, Djaldetti M, Bessler H (2007) Lycopene affects proliferation and apoptosis of four malignant cell lines. Biomed Pharmacother 61:366–369

    Article  CAS  Google Scholar 

  2. Bansal P, Gupta SK, Ojha SK, Nandave M, Mittal R, Kumari S, Arya DS (2006) Cardioprotective effect of lycopene in the experimental model of myocardial ischemia–reperfusion injury. Mol Cell Biochem 289:1–9

    Article  CAS  Google Scholar 

  3. Rao LG, Mackinnon ES, Josse RG, Murray TM, Strauss A, Rao AV (2007) Lycopene consumption decreases oxidative stress and bone resorption markers in postmenopausal women. Osteoporosis Int 18:109–115

    Article  CAS  Google Scholar 

  4. Rao AV, Rao LG (2007) Carotenoids and human health. Pharmacol Res 55:207–216

    Article  CAS  Google Scholar 

  5. Liu QN, Zhu LW, Wang YH, Li DS, Wan DJ, Tang YJ (2009) Advance on the production of lycopene by microbial fermentation. Food Ferment Ind 35:157–161 (In Chinese)

    Google Scholar 

  6. Choudhari SM, Ananthanarayan L, Singhal RS (2008) Use of metabolic stimulators and inhibitors for enhanced production of β-carotene and lycopene by Blakeslea trispora NRRL 2895 and 2896. Bioresour Technol 99:3166–3173

    Article  CAS  Google Scholar 

  7. Fraser PD, Ruiz-Hidalgo MJ, Lopez-Matas MA, Alvarez MI, Eslava AP, Bramley PM (1996) Carotenoid biosynthesis in wild type and mutant strains of Mucor circinelloides. Biochim Biophys Acta 1289:203–208

    Article  Google Scholar 

  8. Miura Y, Kondo K, Saito T, Shimada H, Fraser PD, Misawa N (1998) Production of the carotenoids lycopene, β-carotene, and astaxanthin in the food yeast Candida utilis. Appl Environ Microbiol 64:1226–1229

    CAS  Google Scholar 

  9. Hsu WJ, Yokoyama H, DeBenedict C (1990) Chemical bioregulation of carotenogenesis in Phycomyces blakesleeanus. Photochemistry 29:2447–2451

    Article  CAS  Google Scholar 

  10. Mantzouridou F, Tsimidou MZ (2008) Lycopene formation in Blakeslea trispora. Chemical aspects of a bioprocess. Trends Food Sci Tech 19:363–371

    Article  CAS  Google Scholar 

  11. Thomas DM, Goodwin TW (1967) Studies on carotenogenesis in Blakeslea trispora-I. General observations on synthesis in mated and unmated strains. Phytochemistry 6:355–360

    Article  CAS  Google Scholar 

  12. Lampila LE, Wallen SE, Bullerman LB (1985) A review of factors affecting biosynthesis of carotenoids by the order Mucorales. Mycopathol 90:65–80

    Article  CAS  Google Scholar 

  13. Pegklidou K, Mantzouridou F, Tsimidou MZ (2008) Lycopene production using Blakeslea trispora in the presence of 2-methyl imidazole: yield, selectivity, and safety aspects. J Agric Food Chem 56:4482–4490

    Article  CAS  Google Scholar 

  14. Papaioannou EH, Liakopoulou-Kyriakides M (2010) Substrate contribution on carotenoids production in Blakeslea trispora cultivations. Food Bioprod Process 88:305–311

    Article  CAS  Google Scholar 

  15. Xu F, Yuan QP, Dong HR (2006) Determination of lycopene and β-carotene by high-performance liquid chromatography using Sudan I as internal standard. J Chromatogr B 838:44–49

    Article  CAS  Google Scholar 

  16. Sutter RP, Capage DA, Harrison TL, Keen WA (1973) Trisporic acid biosynthesis in separate plus and minus cultures of Blakeslea trispora: identification by Mucor assay of two mating-type-specific components. J Bacteriol 114:1074–1082

    CAS  Google Scholar 

  17. Sutter RP, Rafelson ME Jr (1968) Separation of β-factor synthesis from stimulated β-carotene synthesis in mated cultures of Blakeslea trispora. J Bacteriol 95:426–432

    CAS  Google Scholar 

  18. Schachtschabel D, David A, Menzel KD, Schimek C, Wöstemeyer J, Boland W (2008) Cooperative biosynthesis of trisporoids by the (+) and (−) mating types of the zygomycete Blakeslea trispora. ChemBioChem 9:3004–3012

    Article  CAS  Google Scholar 

  19. Burmester A, Richter M, Schultze K, Voelz K, Schachtschabel D, Boland W, Wöstemeyer J, Schimek C (2007) Cleavage of β-carotene as the first step in sexual hormone synthesis in zygomycetes is mediated by a trisporic acid regulated β-carotene oxygenase. Fungal Genet Biol 44:1096–1108

    Article  CAS  Google Scholar 

  20. Kuzina V, Cerdá-Olmedo E (2006) Modification of sexual development and carotene production by acetate and other small carboxylic acids in Blakeslea trispora and Phycomyces blakesleeanus. Appl Environ Microbiol 72:4917–4922

    Article  CAS  Google Scholar 

  21. Desai HG, Modi VV (1977) Stimulation of carotenogenesis by penicillin in Blakeslea trispora. Phytochem 16:1373–1376

    Article  CAS  Google Scholar 

  22. Rao S, Modi VV (1977) Carotenogenesis: possible mechanism of action of trisporic acid in Blakeslea trispora. Cell Mol Life Sci 33:31–33

    Article  CAS  Google Scholar 

  23. Schachtschabel D, Menzel KD, Krauter G, David A, Roth M, Horn U, Boland W, Wöstemeyer J, Schimek C (2010) Production and derivate composition of trisporoids in extended fermentation of Blakeslea trispora. Appl Microbiol Biotechnol 88:241–249

    Article  CAS  Google Scholar 

  24. Dandekar S, Modi VV, Jani UK (1980) Chemical regulators of carotenogenesis by Blakeslea trispora. Phytochemistry 19:795–798

    Article  CAS  Google Scholar 

  25. Schmidt AD, Heinekamp T, Matuschek M, Liebmann B, Bollschweiler C, Brakhage AA (2005) Analysis of mating-dependent transcription of Blakeslea trispora carotenoid biosynthesis genes carB and carRA by quantitative real-time PCR. Appl Microbiol Biotechnol 67:549–555

    Article  CAS  Google Scholar 

  26. Debieu D, Bach J, Arnold A, Brousset S, Gredt M, Taton M, Rahier A, Malosse C, Leroux P (2000) Inhibition of ergosterol biosynthesis by morpholine, piperidine, and spiroketalamine fungicides in Microdochium nivale: effect on sterol composition and sterol ∆8 → ∆7-isomerase activity. Pestic Biochem Physiol 67:85–94

    Article  CAS  Google Scholar 

  27. Mehta BJ, Obraztsova IN, Cerdá-Olmedo E (2003) Mutants and intersexual heterokaryons of Blakeslea trispora for production of β-carotene and lycopene. Appl Environ Microbiol 69:4043–4048

    Article  CAS  Google Scholar 

  28. Liu XJ, Liu RS, Li HM, Tang YJ (2011) Scale-up study on the mated fermentation of Blakeslea trispora NRRL 2895 (+) and 2896 (−) for the production of lycopene in the stirred-tank bioreactor. Process Biochem (in submission)

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Acknowledgments

Financial support from the National Natural Science Foundation of China (NSFC, Project Nos. 20976038 and 21176059), the Key Project of Chinese Ministry of Education (Project No. 210132), Hubei Provincial Natural Science Foundation for Innovative Research Team (Project No. 2008CDA002), Scientific Research Key Project of Hubei Provincial Department of Education (Project No. Z20101401), Discipline Leader Project of Wuhan Municipality (Project No. 200951830553), Key Technology R&D Program of Wuhan Municipality (Project No. 201120822280-2), the Open Project Programs for the Key Laboratory of Fermentation Engineering (Ministry of Education), the National Key Laboratory of Biochemical Engineering (Project No. 2010KF-06), and the State Key Laboratory of Bioreactor Engineering are gratefully acknowledged. Ya-Jie Tang also thanks the Chutian Scholar Program (Hubei Provincial Department of Education, China) (2006).

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Authors and Affiliations

  1. Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan, 430068, China

    Jin-Feng Wang, Xiu-Ji Liu, Rui-Sang Liu, Hong-Mei Li & Ya-Jie Tang

  2. Lab of Biorefinery Engineering, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201203, China

    Ya-Jie Tang

  3. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100080, China

    Ya-Jie Tang

  4. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China

    Ya-Jie Tang

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  1. Jin-Feng Wang
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Correspondence to Ya-Jie Tang.

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Wang, JF., Liu, XJ., Liu, RS. et al. Optimization of the mated fermentation process for the production of lycopene by Blakeslea trispora NRRL 2895 (+) and NRRL 2896 (−). Bioprocess Biosyst Eng 35, 553–564 (2012). https://doi.org/10.1007/s00449-011-0628-6

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  • DOI: https://doi.org/10.1007/s00449-011-0628-6

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