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Dihydrophenylalanine: a prephenate-derived Photorhabdus luminescens antibiotic and intermediate in dihydrostilbene biosynthesis.

Publication ,  Journal Article
Crawford, JM; Mahlstedt, SA; Malcolmson, SJ; Clardy, J; Walsh, CT
Published in: Chemistry & biology
September 2011

2,5-Dihydrophenylalanine (H(2)Phe) is a multipotent nonproteinogenic amino acid produced by various Actinobacteria and Gammaproteobacteria. Although the metabolite was discovered over 40 years ago, details of its biosynthesis have remained largely unknown. We show here that L-H(2)Phe is a secreted metabolite in Photorhabdus luminescens cultures and a precursor of a recently described 2,5-dihydrostilbene. Bioinformatic analysis suggested a candidate gene cluster for the processing of prephenate to H(2)Phe, and gene knockouts validated that three adjacent genes plu3042-3044 were required for H(2)Phe production. Biochemical experiments validated Plu3043 as a nonaromatizing prephenate decarboxylase generating an endocyclic dihydro-hydroxyphenylpyruvate. Plu3042 acted next to transaminate the Plu3043 product, precluding spontaneous exocyclic double-bond isomerization and yielding 2,5-dihydrotyrosine. The enzymatic products most plausibly on path to H(2)Phe illustrate the versatile metabolic rerouting of prephenate from aromatic amino acid synthesis to antibiotic synthesis.

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Published In

Chemistry & biology

DOI

EISSN

1879-1301

ISSN

1074-5521

Publication Date

September 2011

Volume

18

Issue

9

Start / End Page

1102 / 1112

Related Subject Headings

  • Recombinant Proteins
  • Photorhabdus
  • Phenylalanine
  • Organic Chemistry
  • Multigene Family
  • Gene Knockout Techniques
  • Cyclohexenes
  • Cyclohexanecarboxylic Acids
  • Bacterial Proteins
  • Anti-Bacterial Agents
 

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Crawford, J. M., Mahlstedt, S. A., Malcolmson, S. J., Clardy, J., & Walsh, C. T. (2011). Dihydrophenylalanine: a prephenate-derived Photorhabdus luminescens antibiotic and intermediate in dihydrostilbene biosynthesis. Chemistry & Biology, 18(9), 1102–1112. https://doi.org/10.1016/j.chembiol.2011.07.009
Crawford, Jason M., Sarah A. Mahlstedt, Steven J. Malcolmson, Jon Clardy, and Christopher T. Walsh. “Dihydrophenylalanine: a prephenate-derived Photorhabdus luminescens antibiotic and intermediate in dihydrostilbene biosynthesis.Chemistry & Biology 18, no. 9 (September 2011): 1102–12. https://doi.org/10.1016/j.chembiol.2011.07.009.
Crawford JM, Mahlstedt SA, Malcolmson SJ, Clardy J, Walsh CT. Dihydrophenylalanine: a prephenate-derived Photorhabdus luminescens antibiotic and intermediate in dihydrostilbene biosynthesis. Chemistry & biology. 2011 Sep;18(9):1102–12.
Crawford, Jason M., et al. “Dihydrophenylalanine: a prephenate-derived Photorhabdus luminescens antibiotic and intermediate in dihydrostilbene biosynthesis.Chemistry & Biology, vol. 18, no. 9, Sept. 2011, pp. 1102–12. Epmc, doi:10.1016/j.chembiol.2011.07.009.
Crawford JM, Mahlstedt SA, Malcolmson SJ, Clardy J, Walsh CT. Dihydrophenylalanine: a prephenate-derived Photorhabdus luminescens antibiotic and intermediate in dihydrostilbene biosynthesis. Chemistry & biology. 2011 Sep;18(9):1102–1112.

Published In

Chemistry & biology

DOI

EISSN

1879-1301

ISSN

1074-5521

Publication Date

September 2011

Volume

18

Issue

9

Start / End Page

1102 / 1112

Related Subject Headings

  • Recombinant Proteins
  • Photorhabdus
  • Phenylalanine
  • Organic Chemistry
  • Multigene Family
  • Gene Knockout Techniques
  • Cyclohexenes
  • Cyclohexanecarboxylic Acids
  • Bacterial Proteins
  • Anti-Bacterial Agents