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Applied Microbiology and Biotechnology

, Volume 77, Issue 4, pp 797–807 | Cite as

Standardized biosynthesis of flavan-3-ols with effects on pancreatic beta-cell insulin secretion

  • Joseph A. Chemler
  • Lye T. Lock
  • Mattheos A. G. KoffasEmail author
  • Emmanuel S. Tzanakakis
Biotechnological Products and Process Engineering

Abstract

Flavan-3-ols, such as green tea catechins represent a major group of phenolic compounds with significant medicinal properties. We describe the construction and optimization of Escherichia coli recombinant strains for the production of mono- and dihydroxylated catechins from their flavanone and phenylpropanoid acid precursors. Use of glucose minimal medium, Fe(II), and control of oxygen availability during shake-flask experiments resulted in production yield increases. Additional production improvement resulted from the use of medium rather than high-copy number plasmids and, in the case of mono-hydroxylated compounds, the addition of extracellular cofactors in the culture medium. The established metabolic engineering approach allowed the biosynthesis of natural catechins at high purity for assessing their possible insulinotropic effects in pancreatic β-cell cultures. We demonstrated that (+)-afzelechin and (+)-catechin modulated the secretion of insulin by pancreatic β-cells. These results indicate the potential of applying metabolic engineering approaches for the synthesis of natural and non-natural catechin analogues as drug candidates in diabetes treatments.

Keywords

Flavonoids Catechins Metabolic engineering Insulin Diabetes Flavan-3-ols. 

Notes

Acknowledgments

We thank the members of the Koffas and Tzanakakis laboratories for helpful discussions. E.S.T. is supported by a J.D. Watson Award from the New York State Foundation for Science, Technology and Innovation (NYSTAR). M.A.G.K. and E.S.T. acknowledge the support received from the New York State Center of Excellence in Bioinformatics and Life Sciences.

Supplementary material

253_2007_1227_MOESM1_ESM.pdf (85 kb)
Supplementary Table 1 Primers used for gene amplification (PDF 87 kb)

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Joseph A. Chemler
    • 1
  • Lye T. Lock
    • 1
  • Mattheos A. G. Koffas
    • 1
    Email author
  • Emmanuel S. Tzanakakis
    • 1
  1. 1.Department of Chemical and Biological EngineeringState University of New York at BuffaloBuffaloUSA

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