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Olive Pomace Oil can be Used as an Alternative Carbon Source for Clavulanic Acid Production by Streptomyces clavuligerus

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Abstract

Clavulanic acid is an important drug, both medically and economically. It is used to combat bacterial resistance to β-lactam antibiotics and is on the World Health Organisation’s List of Essential Medicines in combination with amoxicillin. An olive oil industry waste product, olive pomace oil (OPO), is a potential alternative carbon source for clavulanic acid production by Streptomyces clavuligerus. OPO is six times cheaper than glycerol, which is the current industry standard. The aims of this study were to examine if OPO can be used as a carbon source for clavulanic acid production and to compare the clavulanic acid yield achieved in shake flasks and 1.8 L bioreactors. It was observed that OPO was efficiently utilised as a sole carbon source by S. clavuligerus growing in a P-limited medium. The S. clavuligerus cells grew faster in OPO-containing cultures compared to the glycerol-containing cultures (control) and produced comparable levels of clavulanic acid, but much earlier. In cultures with ISP2 medium that contained glycerol or OPO, higher levels of clavulanic acid were obtained in shake flask cultures with OPO. Interestingly, the same levels of clavulanic acid were observed in oil-containing cultures in bioreactors, but 48 h earlier. Furthermore, the oil-containing cultures did not need addition of an antifoam agent, while higher levels of cell viability were maintained after 72 h in these fermentations compared to the cultures that contained glycerol. Our results suggest that OPO can replace glycerol for clavulanic acid production in S. clavuligerus fermentations, which will significantly increase the productivity and cut the cost for industrial clavulanic acid biosynthesis. The same carbon source can be tested in other similar fermentation approaches for the production of antibiotics or other valuable bioproducts.

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References

  1. Drawz, S., Bonomo, R.: Three decades of β-lactamase inhibitors. Clin. Microbiol. Rev. 23, 160–201 (2010)

    Article  Google Scholar 

  2. World Health Organisation: WHO Model List of Essential Medicines 20th List. World Health Organisation (2017)

  3. Paradkar, A.: Clavulanic acid production by Streptomyces clavuligerus: biogenesis, regulation, and strain improvement. J. Antibiot. 66, 411–420 (2013)

    Article  Google Scholar 

  4. Pérez-Redondo, R., Santamarta, I., Bovenberg, R., Martin, J., Liras, P.: The enigmatic lack of glucose utilization in Streptomyces clavuligerus is due to inefficient expression of the glucose permease gene. Microbiology 156, 1527–1537 (2010)

    Article  Google Scholar 

  5. Costa, C.L.L., Badino, A.C.: Production of clavulanic acid by Streptomyces clavuligerus in batch cultures without and with glycerol pulses under different temperature conditions. Biochem. Eng. J. 69, 1–7 (2012)

    Article  Google Scholar 

  6. Efthimiou, G., Thumser, A., Avignone-Rossa, C.: A novel finding that Streptomyces clavuligerus can produce the antibiotic clavulanic acid using olive oil as a sole carbon source. J. Appl. Microbiol. 105, 2058–2064 (2008)

    Article  Google Scholar 

  7. Roig, A., Cayuela, M.L., Sánchez-Monedero, M.A.: An overview on olive mill wastes and their valorisation methods. Waste Manag. 26, 960–969 (2006)

    Article  Google Scholar 

  8. Paredes, M.J., Moreno, E., Ramos-Cormenzana, A., Martinez, J.: Characteristics of soil after pollution with waste waters from olive oil extraction plants. Chemosphere 16, 1557–1564 (1987)

    Article  Google Scholar 

  9. DellaGreca, M., Monaco, P., Pinto, G., Pollio, A., Previtera, L., Temussi, F.: Phytotoxicity of low-molecular-weight phenols from olive mill waste waters. Bull. Environ. Contam. Toxicol. 67, 352–359 (2001)

    Article  Google Scholar 

  10. Moghaddam, G., Heyden, Y.V., Rabiei, Z., Sadeghi, N., Oveisi, M.R., Jannat, B., Araghi, V., Hassani, S., Behzad, M., Hajimahmoodi, M.: Characterisation of different olive pulp and kernel oils. J. Food Compos. Anal. 28, 54–60 (2012)

    Article  Google Scholar 

  11. Miranda, T., Esteban, A., Rojas, S., Montero, I., Ruiz, A.: Combustion analysis of different olive residues. Int. J. M. Sci. 9, 512–525 (2008)

    Article  Google Scholar 

  12. Large, K.P., Ison, A.P., Williams, D.J.: The effect of agitation rate on lipid utilisation and clavulanic acid production in Streptomyces clavuligerus. J. Biotechnol. 63, 111–119 (1998)

    Article  Google Scholar 

  13. Korbekandi, H., Darkhal, P., Hojati, Z., Abedi, D., Hamedi, J., Pourhosein, M.: Overproduction of clavulanic acid by UV mutagenesis of Streptomyces clavuligerus. Iran. J. Pharm. Res. 9, 177–181 (2010)

    Google Scholar 

  14. Medema, M.H., Alam, M.T., Breitling, R., Takano, E.: The future of industrial antibiotic production: from random mutagenesis to synthetic biology. Bioeng. Bugs 2, 230–233 (2011)

    Article  Google Scholar 

  15. Kim, S., Kim, J., Shin, C., Park, H.W., Kim, C.: An approach to strain improvement and enhanced production of clavulanic acid in Streptomyces clavuligerus. Biosci. Biotech. Biochem. 73, 160–164 (2009)

    Article  Google Scholar 

  16. Bird, A.E., Bellis, J.M., Gasson, B.C.: Spectrophotometric assay of clavulanic acid by reaction with imidazole. Analyst 107, 1241–1245 (1982)

    Article  Google Scholar 

  17. Martin, J.F.: Phosphate control of the biosynthesis of antibiotics and other secondary metabolites is mediated by the PhoR-PhoP system: an unfinished story. J. Bacteriol. 186, 5197–5201 (2004)

    Article  Google Scholar 

  18. Salem-Berkhit, M.M., Alanazi, F.K., Alsarra, I.A.: Improvement and enhancement of clavulanic acid production in Streptomyces clavuligerus using vegetable oils. Afr. J. Biotechnol. 9, 6806–6812 (2010)

    Google Scholar 

  19. Lee, P.C., Ho, C.C.: Production of clavulanic acid and cephamycin C by Streptomyces clavuligerus in palm-oil medium. World J. Microbiol. Biotechnol. 12, 73–75 (1996)

    Article  Google Scholar 

  20. Ser, H., Law, J.W., Chaiyakunapruk, N., Jacob, S.A., Palanisamy, U.D., Chan, K., Goh, B., Lee, L.: Fermentation conditions that affect clavulanic acid production in Streptomyces clavuligerus: a systematic review. Front. Microbiol. 7, 522 (2016)

    Google Scholar 

  21. Routledge, S.J.: Beyond de-foaming: the effects of antifoams on bioprocess productivity. Comput. Struct. Biotechnol. J. 3, e201210014 (2012)

    Article  Google Scholar 

  22. Bellao, C., Antonio, T., Araujo, M.L.G.C., Badino, A.C.: Production of clavulanic acid and cephamycin C by Streptomyces clavuligerus under different fed-batch conditions. Braz. J. Chem. Eng. 30, 257–266 (2013)

    Article  Google Scholar 

  23. Moral, P.S., Méndez, M.V.R.: Production of pomace olive oil. Grasas Aceites 57, 47–55 (2006)

    Google Scholar 

  24. Anderson, R.F., Tornqvist, E.G.M., Peterson, W.H.: Effect of oil in pilot plant fermentations. J. Agric. Food Chem. 4, 556–559 (1956)

    Article  Google Scholar 

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Correspondence to Georgios Efthimiou.

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Young, T., Li, Y. & Efthimiou, G. Olive Pomace Oil can be Used as an Alternative Carbon Source for Clavulanic Acid Production by Streptomyces clavuligerus. Waste Biomass Valor 11, 3965–3970 (2020). https://doi.org/10.1007/s12649-019-00719-5

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