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Heterologous production of flavanones in Escherichia coli: potential for combinatorial biosynthesis of flavonoids in bacteria

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Journal of Industrial Microbiology and Biotechnology

Abstract

Chalcones, the central precursor of flavonoids, are synthesized exclusively in plants from tyrosine and phenylalanine via the sequential reaction of phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-coumarate:coenzyme A ligase (4CL) and chalcone synthase (CHS). Chalcones are converted into the corresponding flavanones by the action of chalcone isomerase (CHI), or non-enzymatically under alkaline conditions. PAL from the yeast Rhodotorula rubra, 4CL from an actinomycete Streptomyces coelicolor A3(2), and CHS from a licorice plant Glycyrrhiza echinata, assembled as artificial gene clusters in different organizations, were used for fermentation production of flavanones in Escherichia coli. Because the bacterial 4CL enzyme attaches CoA to both cinnamic acid and 4-coumaric acid, the designed biosynthetic pathway bypassed the C4H step. E. coli carrying one of the designed gene clusters produced about 450 μg naringenin/l from tyrosine and 750 μg pinocembrin/l from phenylalanine. The successful production of plant-specific flavanones in bacteria demonstrates the usefulness of combinatorial biosynthesis approaches not only for the production of various compounds of plant and animal origin but also for the construction of libraries of "unnatural" natural compounds.

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Acknowledgements

The work from this laboratory was supported by a Research Grant of the Noda Institute for Scientific Research, by the Bio Design Program of the Ministry of Agriculture, Forestry, and Fisheries of Japan (BDP-03-VI-2–2), and by a grant from the Industrial Technology Research Grant Program 2000 of the New Energy and Industrial Technology Development Organization of Japan (00A03004).

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  1. Department of Biotechnology , The University of Tokyo, Graduate School of Agriculture and Life Sciences, Bunkyo-ku, 113–8657, Tokyo , Japan

    Masafumi Kaneko, Eui Il Hwang, Yasuo Ohnishi & Sueharu Horinouchi

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  1. Masafumi Kaneko
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  2. Eui Il Hwang
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  3. Yasuo Ohnishi
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  4. Sueharu Horinouchi
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Correspondence to Sueharu Horinouchi.

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Dedicated to Professor Sir David Hopwood.

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Kaneko, M., Hwang, E.I., Ohnishi, Y. et al. Heterologous production of flavanones in Escherichia coli: potential for combinatorial biosynthesis of flavonoids in bacteria. J IND MICROBIOL BIOTECHNOL 30, 456–461 (2003). https://doi.org/10.1007/s10295-003-0061-1

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  • DOI: https://doi.org/10.1007/s10295-003-0061-1

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