Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Significantly Enhanced Production of Acarbose in Fed-Batch Fermentation with the Addition of S-Adenosylmethionine

  • Sun, Li-Hui (Institute of Bioengineering, Zhejiang University of Technology) ;
  • Li, Ming-Gang (Institute of Bioengineering, Zhejiang University of Technology) ;
  • Wang, Yuan-Shan (Institute of Bioengineering, Zhejiang University of Technology) ;
  • Zheng, Yu-Guo (Institute of Bioengineering, Zhejiang University of Technology)
  • Received : 2011.11.17
  • Accepted : 2012.01.19
  • Published : 2012.06.28
Download PDF
⟨ Previous Next ⟩

Abstract

Acarbose, a pseudo-oligosaccharide, is widely used clinically in therapies for non-insulin-dependent diabetes. In the present study, S-adenosylmethionine (SAM) was added to selected media in order to investigate its effect on acarbose fermentation by Actinoplanes utahensis ZJB-08196. Acarbose titer was seen to increase markedly when concentrations of SAM were added over a period of time. The effects of glucose and maltose on the production of acarbose were investigated in both batch and fed-batch fermentation. Optimal acarbose production was observed at relatively low glucose levels and high maltose levels. Based on these results, a further fed-batch experiment was designed so as to enhance the production of acarbose. Fed-batch fermentation was carried out at an initial glucose level of 10 g/l and an initial maltose level of 60 g/l. Then, 12 h post inoculation, 100 ${\mu}mol/l$ SAM was added. In addition, 8 g/l of glucose was added every 24 h, and 20 g/l of maltose was added at 96 h. By way of this novel feeding strategy, the maximum titer of acarbose achieved was 6,113 mg/l at 192 h. To our knowledge, the production level of acarbose achieved in this study is the highest ever reported.

Keywords

References

  1. Beunink, J., M. Schedel, and U. Steiner. 2000. Osmotically controlled fermentation process for the preparation of acarbose. U. S. Patent 6,130,072.
  2. Bowers, S. G., T. Mahmud, and H. G. Floss. 2002. Biosynthetic studies on the -${\alpha}$-glucosidase inhibitor acarbose: The chemical synthesis of dTDP-4-amino-4,6-dideoxy-${\alpha}$-D-glucose. Carbohydr. Res. 337: 297-304. https://doi.org/10.1016/S0008-6215(01)00323-8
  3. Brunkhorst, C. and E. Schneider. 2005. Characterization of maltose and maltotriose transport in the acarbose-producing bacterium Actinoplanes sp. Res. Microbiol. 156: 851-857. https://doi.org/10.1016/j.resmic.2005.03.008
  4. Choi, B. T. and C. S. Shin. 2003. Reduced formation of byproduct component C in acarbose fermentation by Actinoplanes sp. CKD485-16. Biotechnol. Prog. 19: 1677-1682. https://doi.org/10.1021/bp034079y
  5. Feng, Z.-H., Y.-S. Wang, and Y.-G. Zheng. 2011. A new microtiter plate-based screening method for microorganisms producing alpha-amylase inhibitors. Biotechnol. Bioprocess Eng. 16: 894-900. https://doi.org/10.1007/s12257-011-0033-7
  6. Flatt, P. M. and T. Mahmud. 2007. Biosynthesis of aminoglycoside antibiotics and related compounds. Nat. Prod. Rep. 24: 358-392. https://doi.org/10.1039/b603816f
  7. Guzman, S., I. Ramos, E. Moreno, B. Ruiz, R. Rodriguez-Sanoja, L. Escalante, et al. 2005. Sugar uptake and sensitivity to carbon catabolite regulation in Streptomyces peucetius var. caesius. Appl. Microbiol. Biotechnol. 69: 200-206. https://doi.org/10.1007/s00253-005-1965-7
  8. Hodgson, D. A. 1982. Glucose repression of carbon source uptake and metabolism in Streptomyces coelicolor A3(2) and its perturbation in mutants resistant to 2-deoxyglucose. J. Gen. Microbiol. 128: 2417-2430.
  9. Huh, J. H., D. J. Kim, X. Q. Zhao, M. Li, Y. Y. Jo, T. M. Yoon, et al. 2004. Widespread activation of antibiotic biosynthesis by S-adenosylmethionine in streptomycetes. FEMS Microbiol. Lett. 238: 439-447. https://doi.org/10.1111/j.1574-6968.2004.tb09787.x
  10. Jiang, W., Y. T. Sheng, Y. M. Cai, M. J. Guo, and J. Chu. 2010. Comprehensive effects of maltose concentration and medium osmotic pressure on acarbose in Actinoplanes sp. fermentation. Chin. J. Pharm. 41: 178-182. [In Chinese]
  11. Kim, D. J., J. H. Huh, Y. Y. Yang, C. M. Kang, I. H. Lee, C. G, Hyun, et al. 2003. Accumulation of S-adenosyl-L-methionine enhances production of actinorhodin but inhibits sporulation in Streptomyces lividans TK23. J. Bacteriol. 185: 592-600. https://doi.org/10.1128/JB.185.2.592-600.2003
  12. Lee, S., B. Sauerbrei, J. Niggemann, and E. Egelkrout. 1997. Biosynthetic studies on the ${\alpha}$-glucosidase inhibitor acarbose in Actinoplanes sp.: Source of the maltose unit. J. Antibiot. 50: 954-960. https://doi.org/10.7164/antibiotics.50.954
  13. Li, K. T., S. J. Wie, L. Huang, and X. Cheng. 2011. An effective and simplified scale-up strategy for acarbose fermentation based on the carbon control. World J. Microbiol. Biotechnol. [In Press]
  14. Mahmud, T., S. Lee, and H. G. Floss. 2001. The biosynthesis of acarbose and validamycin. Chem. Rec. 1: 300-310. https://doi.org/10.1002/tcr.1015
  15. Okamoto, S., A. Lezhava, T. Hosaka, Y. Okamoto-Hosoya, and K. Ochi. 2003. Enhanced expression of S-adenosylmethionine synthetase causes overproduction of actinorhodin in Streptomyces coelicolor A3(2). J. Bacteriol. 185: 601-609. https://doi.org/10.1128/JB.185.2.601-609.2003
  16. Rockser, Y. and U. F. Wehmeier. 2009. The gac-gene cluster for the production of acarbose from Streptomyces glaucescens GLA.O: Identification, isolation and characterization. J. Biotechnol. 140: 114-123. https://doi.org/10.1016/j.jbiotec.2008.10.016
  17. Saito, N., K. Kurosawa, J. Xu, S. Okamoto, and K. Ochi. 2003. Effect of S-adenosylmethionine on antibiotic production in Streptomyces griseus and Streptomyces griseoflavus. Actinomycetologica 17: 47-49. https://doi.org/10.3209/saj.17_47
  18. Sanchez, S., A. Chavez, A. Forero, Y. Garcia-Huante, A. Romero, M. Sanchez, et al. 2010. Carbon source regulation of antibiotic production. J. Antibiot. 63: 442-459. https://doi.org/10.1038/ja.2010.78
  19. Shin, S. K., D. Xu, H. J. Kwon, and J. W. Suh. 2006. S-Adenosylmethionine activates adpA transcription and promotes streptomycin biosynthesis in Streptomyces griseus. FEMS Microbiol. Lett. 259: 53-59. https://doi.org/10.1111/j.1574-6968.2006.00246.x
  20. Shin, S. K., H. S. Park, H. J. Kwon, H. J. Yoon, and J. W. Suh. 2007. Genetic characterization of two S-adenosylmethionine-induced ABC transporters reveals their roles in modulations of secondary metabolism and sporulation in Streptomyces coelicolor M145. J. Microbiol. Biotechnol. 17: 1818-1825.
  21. Wang, Y.-J., L.-L. Liu, Y.-S. Wang, Y.-P. Xue, Y.-G. Zheng, and Y.-C. Shen. 2012. Actinoplanes utahensis ZJB-08196 fed-batch fermentation at elevated osmolality for enhancing acarbose production. Bioresour. Technol. 103: 337-342. https://doi.org/10.1016/j.biortech.2011.09.121
  22. Wang, Y.-J., L.-L. Liu, Z.-H. Feng, Z.-Q. Liu, and Y.-G. Zheng. 2011. Optimization of media composition and culture conditions for acarbose production by Actinoplanes utahensis ZJB-08196. World J. Microbiol. Biotechnol. 27: 2759-2766. https://doi.org/10.1007/s11274-011-0751-1
  23. Wehmeier, U. F. and W. Piepersberg. 2004. Biotechnology and molecular biology of the alpha-glucosidase inhibitor acarbose. Appl. Microbiol. Biotechnol.63: 613-625. https://doi.org/10.1007/s00253-003-1477-2
  24. Zhang, C. S., M. Podeschwa, O. Block, H. J. Altenbach, W. Piepersberg, and U. F. Wehmeier. 2003. Identification of a 1-epi-valienol 7-kinase activity in the producer of acarbose, Actinoplanes sp. SE50/110. FEMS Lett. 540: 53-57.
  25. Zhao, X. Q., B. Gust, and L. Heide. 2010. S-Adenosylmethionine (SAM) and antibiotic biosynthesis: Effect of external addition of SAM and of overexpression of SAM biosynthesis genes in novobiocin production in Streptomyces. Arch. Microbiol. 192: 289-297. https://doi.org/10.1007/s00203-010-0548-x
  26. Zhao, X. Q., Y. Y. Jin, H. J. Kwon, Y. Y. Yang, and J. W. Suh. 2006. S-Adenosylmethionine (SAM) regulates antibiotic biosynthesis in Streptomyces spp. in a mode independent of its role as a methyl donor. J. Microbiol. Biotechnol. 16: 927-932.

Cited by

  1. Enhanced Production of Acarbose and Concurrently Reduced Formation of Impurity C by Addition of Validamine in Fermentation of Actinoplanes utahensis ZJB-08196 vol.2013, pp.None, 2012, https://doi.org/10.1155/2013/705418
  2. New strategies for drug discovery: activation of silent or weakly expressed microbial gene clusters vol.97, pp.1, 2012, https://doi.org/10.1007/s00253-012-4551-9
  3. Reconstruction and in silico analysis of an Actinoplanes sp. SE50/110 genome-scale metabolic model for acarbose production vol.6, pp.None, 2012, https://doi.org/10.3389/fmicb.2015.00632
  4. Improving acarbose production and eliminating the by-product component C with an efficient genetic manipulation system of Actinoplanes sp. SE50/110 vol.2, pp.4, 2012, https://doi.org/10.1016/j.synbio.2017.11.005
  5. Enhanced acarbose production by Streptomyces M37 using a two-stage fermentation strategy vol.12, pp.2, 2017, https://doi.org/10.1371/journal.pone.0166985
  6. A severe leakage of intermediates to shunt products in acarbose biosynthesis vol.11, pp.1, 2012, https://doi.org/10.1038/s41467-020-15234-8