| Dihydrophenylalanine: A Prephenate-Derived Photorhabdus luminescens Antibiotic and Intermediate in Dihydrostilbene Biosynthesis. | |
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MedLine Citation:
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PMID: 21944749 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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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Authors:
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Jason M Crawford; Sarah A Mahlstedt; Steven J Malcolmson; Jon Clardy; Christopher T Walsh |
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Publication Detail:
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Type: - |
Journal Detail:
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Title: Chemistry & biology Volume: 18 ISSN: 1879-1301 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9500160 Medline TA: Chem Biol Country: - |
Other Details:
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Languages: ENG Pagination: 1102-1112 Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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