DOI QR코드

DOI QR Code

Enhanced Flavonoid Production in Streptomyces venezuelae via Metabolic Engineering

  • Park, Sung-Ryeol (Department of Chemistry and Nano Science, Ewha Womans University) ;
  • Ahn, Mi-Sun (Department of Chemistry and Nano Science, Ewha Womans University) ;
  • Han, Ah-Reum (Department of Chemistry and Nano Science, Ewha Womans University) ;
  • Park, Je-Won (Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction, Sun Moon University) ;
  • Yoon, Yeo-Joon (Department of Chemistry and Nano Science, Ewha Womans University)
  • Received : 2011.08.08
  • Accepted : 2011.08.23
  • Published : 2011.11.28

Abstract

Metabolic engineering of plant-specific phenylpropanoid biosynthesis has attracted an increasing amount of attention recently, owing to the vast potential of flavonoids as nutraceuticals and pharmaceuticals. Recently, we have developed a recombinant Streptomyces venezuelae as a heterologous host for the production of flavonoids. In this study, we successfully improved flavonoid production by expressing two sets of genes predicted to be involved in malonate assimilation. The introduction of matB and matC encoding for malonyl-CoA synthetase and the putative dicarboxylate carrier protein, respectively, from Streptomyces coelicolor into the recombinant S. venezuelae strains expressing flavanone and flavone biosynthetic genes resulted in enhanced production of both flavonoids.

Keywords

References

  1. Hughes, A. J. and A. Keatinge-Clay. 2011. Enzymatic extender unit generation for in vitro polyketide synthase reactions: Structural and functional showcasing of Streptomyces coelicolor MatB. Chem. Biol. 18: 165-176. https://doi.org/10.1016/j.chembiol.2010.12.014
  2. Jung, W. S., S. K. Lee, J. S. J. Hong, S. R. Park, S. J. Jeong, A. R. Han, et al. 2006. Heterologous expression of tylosin polyketide synthase and production of a hybrid bioactive macrolide in Streptomyces venezuelae. Appl. Microbiol. Biotechnol. 72: 763- 769. https://doi.org/10.1007/s00253-006-0318-5
  3. Jung, W. S., S. J. Jeong, S. R. Park, C. Y. Choi, B. C. Park, J. W. Park, and Y. J. Yoon. 2008. Enhanced heterologous production of desosaminyl macrolides and their hydroxylated derivatives by overexpression of the pikD regulatory gene in Streptomyces venezuelae. Appl. Environ. Microbiol. 74: 1972-1979. https://doi.org/10.1128/AEM.02296-07
  4. Kieser, T. M., M. J. Bibb, M. J. Buttner, K. F. Chater, and D. A. Hoopwood. 2000. Practical Streptomyces Genetics. John Innes Foundation, Norwich, England.
  5. Leonard, E., Y. Yan, Z. L. Fowler, Z. Li, C. G. Lim, K. H. Lim, and M. A. Koffas. 2008. Strain improvement of recombinant Escherichia coli for efficient production of plant flavonoids. Mol. Pharm. 5: 257-265. https://doi.org/10.1021/mp7001472
  6. Lombo, F., B. Pfeifer, T. Leaf, S. Ou, Y. S. Kim, D. E. Cane, P. Licari, and C. Khosla. 2001. Enhancing the atom economy of polyketide biosynthetic processes through metabolic engineering. Biotechnol. Prog. 17: 612-617. https://doi.org/10.1021/bp010045j
  7. Park, S. R., J. H. Paik, M. S. Ahn, J. W. Park, and Y. J. Yoon. 2010. Biosynthesis of plant-specific flavones and flavonols in Streptomyces venezuelae. J. Microbiol. Boitechnol. 20: 1295- 1299. https://doi.org/10.4014/jmb.1005.05038
  8. Park, S. R., J. A. Yoon, J. H. Paik, J. W. Park, W. S. Jung, Y. H. Ban, et al. 2009. Engineering of plant-specific phenylpropanoids biosynthesis in Streptomyces venezuelae. J. Biotechnol. 141: 181-188. https://doi.org/10.1016/j.jbiotec.2009.03.013
  9. Quideau, S., D. Deffieux, C. Douat-Casassus, and L. Pouységu. 2011. Plant polyphenols: Chemical properties, biological activities, and synthesis. Angew. Chem. Int. Ed. Engl. 50: 586-621. https://doi.org/10.1002/anie.201000044
  10. Weisshaar, B. and G. I. Jenkins. 1998. Phenylpropanoid biosynthesis and its regulation. Curr. Opin. Plant Biol. 1: 251- 257. https://doi.org/10.1016/S1369-5266(98)80113-1
  11. Winkel-Shirley, B. 2001. Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology. Plant Physiol. 126: 485-493. https://doi.org/10.1104/pp.126.2.485
  12. Yao, L. H., Y. M. Jiang, J. Shi, F. A. Tomas-Barberan, N. Datta, R. Singanusong, and S. S. Chen. 2004. Flavonoids in food and their health benefits. Plant Foods Hum. Nutr. 59: 113-122. https://doi.org/10.1007/s11130-004-0049-7

Cited by

  1. Alkaloids and Flavonoids of Aerial Parts ofIpomea pes-tigridis(Convolvulaceae) are Potential Inhibitors ofStaphylococcus epidermidisandPropionibacterium acnes vol.18, pp.4, 2011, https://doi.org/10.1080/10496475.2012.715118
  2. Towards a new science of secondary metabolism vol.66, pp.7, 2013, https://doi.org/10.1038/ja.2013.25
  3. Production of 3-O-xylosyl quercetin in Escherichia coli vol.97, pp.5, 2011, https://doi.org/10.1007/s00253-012-4438-9
  4. Biosynthesis of Pinocembrin from Glucose Using Engineered Escherichia coli vol.24, pp.11, 2011, https://doi.org/10.4014/jmb.1406.06011
  5. Iterative marker excision system vol.98, pp.10, 2014, https://doi.org/10.1007/s00253-014-5523-z
  6. Overexpression of ribosome recycling factor is responsible for improvement of nucleotide antibiotic-toyocamycin in Streptomyces diastatochromogenes 1628 vol.98, pp.11, 2011, https://doi.org/10.1007/s00253-014-5573-2
  7. A plant malonyl-CoA synthetase enhances lipid content and polyketide yield in yeast cells vol.98, pp.12, 2011, https://doi.org/10.1007/s00253-014-5612-z
  8. Microbial biosynthesis of medicinally important plant secondary metabolites vol.31, pp.11, 2011, https://doi.org/10.1039/c4np00057a
  9. Developing Streptomyces venezuelae as a cell factory for the production of small molecules used in drug discovery vol.38, pp.9, 2011, https://doi.org/10.1007/s12272-015-0638-z
  10. Heterologous expression of oxytetracycline biosynthetic gene cluster in Streptomyces venezuelae WVR2006 to improve production level and to alter fermentation process vol.100, pp.24, 2011, https://doi.org/10.1007/s00253-016-7873-1
  11. Engineering microbial hosts for production of bacterial natural products vol.33, pp.8, 2016, https://doi.org/10.1039/c6np00017g
  12. Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology vol.34, pp.5, 2016, https://doi.org/10.1016/j.biotechadv.2016.02.012
  13. The acyl-activating enzyme PhAAE13 is an alternative enzymatic source of precursors for anthocyanin biosynthesis in petunia flowers vol.68, pp.3, 2011, https://doi.org/10.1093/jxb/erw426
  14. De Novo Biosynthesis of Apigenin, Luteolin, and Eriodictyol in the Actinomycete Streptomyces albus and Production Improvement by Feeding and Spore Conditioning vol.8, pp.None, 2011, https://doi.org/10.3389/fmicb.2017.00921
  15. Engineering microbial cell factories for the production of plant natural products: from design principles to industrial-scale production vol.16, pp.None, 2017, https://doi.org/10.1186/s12934-017-0732-7
  16. Production of plant-derived polyphenols in microorganisms: current state and perspectives vol.102, pp.4, 2011, https://doi.org/10.1007/s00253-018-8747-5
  17. Challenges in the microbial production of flavonoids vol.17, pp.2, 2011, https://doi.org/10.1007/s11101-017-9515-3
  18. Metabolic engineering of glycosylated polyketide biosynthesis vol.2, pp.3, 2018, https://doi.org/10.1042/etls20180011
  19. De novo biosynthesis of myricetin, kaempferol and quercetin in Streptomyces albus and Streptomyces coelicolor vol.13, pp.11, 2018, https://doi.org/10.1371/journal.pone.0207278
  20. Recent advancement of engineering microbial hosts for the biotechnological production of flavonoids vol.46, pp.6, 2011, https://doi.org/10.1007/s11033-019-05066-1
  21. Streptomyces as Microbial Chassis for Heterologous Protein Expression vol.9, pp.None, 2011, https://doi.org/10.3389/fbioe.2021.804295
  22. Coordinating precursor supply for pharmaceutical polyketide production in Streptomyces vol.69, pp.None, 2011, https://doi.org/10.1016/j.copbio.2020.11.006
  23. De novo biosynthesis of garbanzol and fustin in Streptomyces albus based on a potential flavanone 3‐hydroxylase with 2‐hydroxylase side activity vol.14, pp.5, 2011, https://doi.org/10.1111/1751-7915.13874
  24. Refactoring of a synthetic raspberry ketone pathway with EcoFlex vol.20, pp.1, 2011, https://doi.org/10.1186/s12934-021-01604-4