Food Science and Biotechnology

, Volume 27, Issue 2, pp 581–590 | Cite as

Statistical optimization of culture medium for improved production of antimicrobial compound by Streptomyces rimosus AG-P1441

  • Yoonjung Ju
  • Kwang-Hee Son
  • Chunzhi Jin
  • Byung Soon Hwang
  • Dong-Jin Park
  • Chang-Jin Kim


The nutritional requirements for antimicrobial activity of Streptomyces rimosus AG-P1441 were optimized using statistically-based experimental designs at a flask level. Based on a one-factor-at-a-time (OFAT) approach, glucose, corn starch and soybean meal were identified as the carbon and nitrogen sources having a significant effect on antimicrobial productivity. As a result of investigating the effect of glucose concentration, the highest antimicrobial activity was observed at 3% concentration. Response surface methodology (RSM) was then applied to optimize the growth medium components (corn starch, soybean meal, MgCl2 and glutamate). Antimicrobial productivity increased sharply when the medium consisted of 3% glucose, 3.5% corn starch, 2.5% soybean meal, 1.2 mM MgCl2 and 5.9 mM glutamate. The fermentation using optimized culture medium in a 5-L bioreactor allowed a significant increase in antimicrobial activity, evaluated by the paper disc assay, revealed a 29 mm inhibition zone diameter against Phytophthora capsici.


Streptomyces rimosus AG-P1441 Phytophthora capsici Biocontrol Medium optimization 



This research was supported by a Grant (10045326) from the R&D Program of MOTIE/KEIT of Republic of Korea, the KRIBB Research Initiative Program, Republic of Korea and a Grant (NRF-2013M3A9A5076601) from a study on the strategies of improving the value of microbial resources funded by Ministry of Science, ICT and Future Planning of the Korea Government.

Supplementary material

10068_2017_257_MOESM1_ESM.docx (445 kb)
Supplementary material 1 (DOCX 445 kb)


  1. 1.
    Hausbeck MK, Lamour KH. Phytophthora capsici on vegetable crops: research progress and management challenges. Plant Dis. 88: 1292–1300 (2014)CrossRefGoogle Scholar
  2. 2.
    Chen YY, Chen PC, Tsay TT. The biocontrol efficacy and antibiotic activity of Streptomyces plicatus on the oomycete Phytophthora capsici. Biol. Control. 98: 34–42 (2016)CrossRefGoogle Scholar
  3. 3.
    Gavino PD, Smart CD, Sandrock RW, Miller JS, Hamm PB, Lee TY, Davis RM, Fry WE. Implications of sexual reproduction for Phytophthora infestans in the United States: generation of an aggressive lineage. Plant Dis. 84: 731–735 (2000)CrossRefGoogle Scholar
  4. 4.
    Zohara F, Akanda AM, Paul NC, Rahman M, Islam T. Inhibitory effects of Pseudomonas spp. on plant pathogen Phytophthora capsici in vitro and in planta. Biocatal. Agric. Biotechnol. 5: 69–77 (2016)Google Scholar
  5. 5.
    Lee HB, Kim Y, Kim JC, Choi GJ, Park SH, Kim CJ, Jung HS. Activity of some aminoglycoside antibiotics against true fungi, Phytophthora and Pythium species. J. Appl. Microbiol. 99: 836–843 (2005)CrossRefGoogle Scholar
  6. 6.
    Rothrock CS and Gottlieb D. Importance of antibiotic production in antagonism of Streptomyces species to two soil-borne plant pathogens. J. Antibiot. 34: 830–835 (1981)CrossRefGoogle Scholar
  7. 7.
    Crawford DL, Linch JM, Whipps JM and Ousley MA. Isolation and characterization of actinomycete antagonists of a fungal root pathogen. Appl. Environ. Microbiol. 59: 3899–3905 (1993)Google Scholar
  8. 8.
    Mari M, Guizzardi M and Pratella GC. Biological control of gray mold in pears by antagonistic bacteria. Biol. Control. 7: 30–37 (1996)CrossRefGoogle Scholar
  9. 9.
    Georgakopoulos DG, Fiddaman P, Leifert C and Malathrakis NE. Biological control of cucumber and sugar beet damping off caused by Pythium ultimum with bacterial and fungal antagonists. J. Appl. Microbiol. 92: 1078–1086 (2002)CrossRefGoogle Scholar
  10. 10.
    Kim CJ, Park DJ, Lee JC, Ju YJ, Yoon BS. Development of biocontrol agent from bioactive compounds of microbial origin. Annual report of Rural Development Administration. (2013)Google Scholar
  11. 11.
    Rathi P, Goswami VK, Sahai V, Gupta R. Statistical medium optimization and production of a hyperthermostable lipase from Burkholderia cepacia in a bioreactor. J. Appl. Microbiol. 93(6): 930–936 (2002)CrossRefGoogle Scholar
  12. 12.
    Grove and Randall. Assay methods of antibiotics medical encyclopedia. Inc. New York, NY, USA. (1955)Google Scholar
  13. 13.
    Singh AK, Mehta G, Chhatpar HS. Optimization of medium constituents for improved chitinase production by Paenibacillus sp. D1 using statistical approach. Lett. Appl. Microbiol. 49(6): 708–714 (2009)CrossRefGoogle Scholar
  14. 14.
    Plackett RL and Burman JP. The design of optimum multifactorial experiments. Biometrika. 33(4): 305–325 (1946)CrossRefGoogle Scholar
  15. 15.
    Box G, Hunter W, Hunter J. Statistics for experiments. Wiley, New York, USA. (1958)Google Scholar
  16. 16.
    Singh V, Haque S, Niwas R, Srivastava A, Pasupuleti M, Tripathi CK. Strategies for Fermentation Medium Optimization: An In-Depth Review. Front. Microbiol. Jan 6;7:2087 (2017)Google Scholar
  17. 17.
    Sánchez S, Chávez A, Forero A, García-Huante Y, Romero A, Sánchez M, Rocha D, Sánchez B, Avalos M, Guzmán-Trampe S, Rodríguez-Sanoja R, Langley E, Ruiz B. Carbon source regulation of antibiotic production. J. Antibiot. 63: 442–459 (2010)CrossRefGoogle Scholar
  18. 18.
    Aharonowitz, Y. Nitrogen metabolite regulation of antibiotic biosynthesis. Ann. Rev. Microbiol. 34: 209–233 (1980)CrossRefGoogle Scholar
  19. 19.
    Porter MA, Jones AM. Variability in soy flour composition. J. Am. Oil Chem. Soc. 80(6): 557–562 (2003)CrossRefGoogle Scholar
  20. 20.
    Schrader KK, Blevins WT. Effects of carbon source, phosphorus concentration, and several micronutrients on biomass and geosmin production by Streptomyces halstedii. J. Ind. Microbiol. Biotechnol. 26(4): 241–247 (2001)CrossRefGoogle Scholar
  21. 21.
    Natsume M, Kamo Y, Hirayama M, Adachi T. Isolation and characterization of alginate-derived oligosaccharides with roof growth-promoting activities. Carbohydr. Res. 258: 187–197 (1994)CrossRefGoogle Scholar
  22. 22.
    Okba AK, Ogata T, Matsubara H, Matsuo S, Doi K, Ogata S. Effects of bacitracin and excess Mg2+ on submerged mycelial growth of Streptomyces azureus. J. Ferment. Bioeng. 86: 28–33 (1998)CrossRefGoogle Scholar
  23. 23.
    Lubbe C, Jensen SE, Demain AL. Prevention of phosphate inhibition of cephalosporin synthetases by ferrous ion. FEMS Microbiol. Lett. 25: 75–79 (1984)CrossRefGoogle Scholar
  24. 24.
    Raza W, Yang XM, Wu HS, Huang QW, Xu YC, Shen QR. Evaluation of metal ions (Zn2+, Fe3+, Mg2+) effect on production of fusaricidin-type antifungal compounds by Paenibacillus polymyxa SQR-2. Bioresour. Technol. 101: 9264–9271 (2010)CrossRefGoogle Scholar
  25. 25.
    Mahmood M. Trace elements for growth and bulbiformin production by Bacillus subtilis. J. Appl. Bacteriol. 35: 1–5 (1972)CrossRefGoogle Scholar
  26. 26.
    Liu CM, McDaniel LE, Schaffner CP. Factors affecting the production of Candicidin. Antimicrob. Agents. Chemother. 7: 196–202 (1975)CrossRefGoogle Scholar
  27. 27.
    Voelker F, Altaba S. Nitrogen source governs the patterns of growth and pristinamycin production in ‘Streptomyces pristinaespiralis’ Microbiology. 147: 2447–2459 (2001)CrossRefGoogle Scholar
  28. 28.
    Sissi C, Palumbo M. Effects of magnesium and related divalent metal ions in topoisomerase structure and function. Nucleic Acids Res. Feb;37(3): 702–711 (2009)Google Scholar
  29. 29.
    Cowan JA. Introduction to the biological chemistry of magnesium ion. The biological chemistry of magnesium. VCH. New York, 1–23 (1995)Google Scholar
  30. 30.
    Box, GEP, Wilson, KB. On the experimental attainment of optimum conditions. J. Roy. Stat. Soc. (Ser. B) 13: 1–45 (1951)Google Scholar
  31. 31.
    Rajeswari P, Jose PA, Amiya R, Jebakumar SR. Characterization of saltern based Streptomyces sp. and statistical media optimization for its improved antibacterial activity. Front. Microbiol. 5: 753 (2015)CrossRefGoogle Scholar
  32. 32.
    Gao H, Liu M, Liu J, Dai H, Zhou X, Liu X, Zhuo Y, Zhang W, Zhang L. Medium optimization for the production of avermectin B1a by Streptomyces avermitilis 14-12A using response surface methodology. Bioresour. Technol. 100: 4012–4016 (2009)CrossRefGoogle Scholar
  33. 33.
    Vineeta Singh, C.K.M. Tripathi. Production and statistical optimization of a novel olivanic acid by Streptomyces olivaceus MTCC 6820. Process biochem. 43: 1313–1317 (2008)CrossRefGoogle Scholar
  34. 34.
    Chen XC, Bai JX, Cao JM, Li ZJ, Xiong J, Zhang L, Hong Y, Ying HJ. Medium optimization for the production of cyclic adenosine 3′,5′-monophosphate by Microbacterium sp. no. 205 using response surface methodology. Bioresour. Technol. 100: 919–924 (2009)CrossRefGoogle Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  • Yoonjung Ju
    • 1
  • Kwang-Hee Son
    • 1
  • Chunzhi Jin
    • 1
    • 2
  • Byung Soon Hwang
    • 1
  • Dong-Jin Park
    • 1
  • Chang-Jin Kim
    • 1
    • 2
  1. 1.Industrial Biomaterial Research CenterKorea Research Institute of Bioscience and BiotechnologyDaejeonKorea
  2. 2.University of Science and TechnologyDaejeonKorea

Personalised recommendations