Hypothemycin production and its derivatives diversifying of Aigialus parvus BCC 5311 influenced by cultural condition


Many metabolites produced by various microorganisms have proven their usefulness in the area concerning human health. However, most of their diverse natural compound biosyntheses are hardly discovered. These metabolites might have specific or novel functions and these diverse active compounds can be achieved by biosynthesis, semi-biosynthesis, or chemical synthesis. A strategy to exploit the biosynthesis potential of a fungal strain is to use various culture conditions and to evaluate the chemical profiles of the culture extracts. The value of this approach was demonstrated with the fungal strain Aigialus parvus BCC 5311, producer of hypothemycin, aigialospirol, and aigialomycin A-D. The optimization of hypothemycin production and its derivative diversity by Aigialus parvus BCC 5311 was carried out using qualitative (general factorial design) and quantitative analysis (two-level fractional factorial design). Qualitative analysis revealed that soluble starch and yeast extract were shown to be the best carbon and nitrogen source respectively for the production of hypothemycin, aigialospirol and aigialomycin A-D. Quantitative analysis showed that the initial pH of culture medium is the most important factor that affects the production of hypothemycin and its derivatives (aigialospirol and aigialomycin A-D) production. Optimal medium composition used in a 5 L bioreactor generated a specific growth rate of A. parvus BCC 5311 of 0.0295 h-1, biomass yield of 1.6 g×gstarch-1, hypothemycin yield of 13.6 mg×gbiomass-1, and hypothemycin production rate of 0.6 mg×L-1×day-1. The maximum concentration of 58.0 mg×L-1 of hypothemycin was obtained at 120 h of culturing. Furthermore, the Aigialomycin A-D and Aigialospirol obtained were diversified towards various cultural conditions used. The high amount of hypothemycin produced and the diversity of derivatives obtained from this study should be useful for future mass production.

Share and Cite:

Kocharin, K. , Supothina, S. and Prathumpa, W. (2013) Hypothemycin production and its derivatives diversifying of Aigialus parvus BCC 5311 influenced by cultural condition. Advances in Bioscience and Biotechnology, 4, 1049-1056. doi: 10.4236/abb.2013.412140.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Fu, X., Albermann, C., Zhang, C. and Thorson, J.S. (2005) Diversifying vancomycin via chemoenzymatic strategies. Organic Letters, 7, 1513-1515.
[2] Knight, V., Sanglier, J.J., Di, T.D., Braccili, S., Bonner, P., Waters, J., Hughes, D. and Zhang, L. (2003) Diversifying microbial natural products for drug discovery. Applied Microbiology and Biotechnology, 62, 446-458.
[3] Umeno, D., Tobias, A.V. and Arnold, F.H. (2005) Diversifying carotenoid biosynthetic pathways by directed evolution. Microbiology and Molecular Biology Reviews, 69, 51-78. http://dx.doi.org/10.1128/MMBR.69.1.51-78.2005
[4] Petit, R.K. (2009) Mixed fermentation for natural product drug discovery. Applied Microbiology and Biotechnology, 9, 1916-1919.
[5] Isaka, M., Suyarnsestakorn, C. and Tanticharoen, M. (2002) Aigialomycin A-E, new resoculicmacrolides from the marine mangrove fungus Aigialus parvus. Journal of Organic Chemistry, 67, 1561-1566.
[6] Nair, M.S.R. and Carey, S.T. (1980) Metabolites of pyrenomycetes, XIV Structure and partial stereochemistry of the antibiotic macrolideshypothemycin and dihydrohypothemycin. Tetrahedron Letters, 21, 2011-2012.
[7] Nair, M.S.R., Carey, S.T. and James, J.C. (1981) Metabolites of pyrenomycetes, XIV: Structure and partial stereochemistry of the antibiotic macrolideshypothemycin and dihydrohypothemycin. Tetrahedron, 37, 2445-2449. http://dx.doi.org/10.1016/S0040-4020(01)88900-6
[8] Schaeffer, H.J. and Weber, M.J. (1999) Mitogen-activated protein kinases: Specific messages from ubiquitous messengers. Molecular and Cellular Biology, 19, 2435-2444.
[9] Robinson, M.J. and Cobb, M.H. (1997) Mitogen-activated protein kinase pathways. Current Opinion in Cell Biology, l9, 180-186.
[10] Camacho, R., Staruch, M.J., DaSilva, C., Koprak, S., Sewell, T., Salituro, G. and Dumont, F.J. (2000) Hypothemycin inhibits the proliferative response and modulates the production of cytokines during T Cell activation. Immunopharmacology, 44, 255-265.
[11] Kolch, W. (2000) Meaningful relationships: The regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochemical Journal, 351, 289-305.
[12] Schirmer, A., Kennedy, J., Murli, S., Reid, R. and Santi, D.V. (2006) Targeted covalent inactivation of protein kinases by resorcylic acid lactone polyketides. Proceedings of the National Academy of Sciences USA, 103, 4234-4239. http://dx.doi.org/10.1073/pnas.0600445103
[13] Wee, J.L., Sundermann, K., Licari, P. and Galazzo, J. (2006) Cytotoxic hypothemycin analogues from Hypomyces subiculosus. Journal of Natural Products, 69, 1456-1459. http://dx.doi.org/10.1021/np060258o
[14] Agatsuma, T., Takahashi, A., Kabuto, C. and Nozoe, S. (1993) Revised structure and stereochemistry of hypothemycin. Chemical & Pharmaceutical Bulletin, 41, 373-375. http://dx.doi.org/10.1248/cpb.41.373
[15] Vongvilai, P., Isaka, M., Kittakoop, P., Srikitikulchai, P., Kongsaeree, P. and Thebtaranonth, Y. (2004) Ketene acetal and spiroacetal constituents of the marine fungus Aigialus parvus BCC 5311. Journal of Natural Products, 67, 457-460. http://dx.doi.org/10.1021/np030344d
[16] Prathumpai, W., Kocharin, K., Phimmakong, K. and Wongsa, P. (2007) Effects of different carbon and nitrogen sources on naphthoquinone production of Cordyceps unilateralis BCC1869. Applied Biochemistry and Biotechnology, 136, 223-232.
[17] Larsen, T.O., Smedsgaard, J., Nielsen, K.F., Hansen, M.E. and Frisvad, J.C. (2005) Phenotypic taxonomy and metabolite profiling in microbial drug discovery. Natural Product Reports, 22, 672-695.

Copyright © 2021 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.