The Rare Fluorinated Natural Products and Biotechnological Prospects for Fluorine Enzymology

K. K. Jason Chan, David O'Hagan*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

49 Citations (Scopus)

Abstract

Nature has hardly evolved a biochemistry of fluorine although there is a low-level occurrence of fluoroacetate found in selected tropical and subtropical plants. This compound, which is generally produced in low concentrations, has been identified in the plants due to its high toxicity, although to date the biosynthesis of fluoroacetate in plants remains unknown. After that, fluorinated entities in nature are extremely rare, and despite increasingly sophisticated screening and analytical methods applied to natural product extraction, it has been 25 years since the last bona fide fluorinated natural product was identified from an organism. This was the reported isolation of the antibiotic 4-fluorothreonine and the toxin fluoroacetate in 1986 from Streptomyces cattleya. This bacterium has proven amenable to biochemical investigation, the fluorination enzyme (fluorinase) has been isolated and characterized, and the biosynthetic pathway to these bacterial metabolites has been elucidated. Also the fluorinase gene has been cloned into a host bacterium (Salinispora tropica), and this has enabled the de novo production of a bioactive fluorinated metabolite from fluoride ion, by genetic engineering. Biotechnological manipulation of the fluorinase offers the prospects for the assembly of novel fluorinated metabolites by fermentation technology. This is particularly attractive, given the backdrop that about 15-20% of pharmaceuticals licensed each year (new chemical entities) contain a fluorine atom.

Original languageEnglish
Title of host publicationNATURAL PRODUCT BIOSYNTHESIS BY MICROORGANISMS AND PLANTS, PT B
EditorsDA Hopwood
Place of PublicationSAN DIEGO
PublisherAcademic Press/Elsevier
Pages219-235
Number of pages17
ISBN (Print)978-0-12-394291-3
DOIs
Publication statusPublished - 2012

Publication series

NameMethods in Enzymology
PublisherELSEVIER ACADEMIC PRESS INC
Volume516
ISSN (Print)0076-6879

Keywords

  • ENZYME
  • STREPTOMYCES-CATTLEYA
  • MECHANISM
  • NUCLEOSIDES
  • IDENTIFICATION
  • BIOSYNTHESIS
  • 4-FLUOROTHREONINE
  • BOND FORMATION
  • DICHAPETALUM-TOXICARIUM
  • CRYSTAL-STRUCTURE

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