Engineering Fluorometabolite Production: Fluorinase Expression in Salinispora tropica Yields Fluorosalinosporamide

Alessandra S. Eustaquio, David O'Hagan*, Bradley S. Moore

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

Abstract

Organofluorine compounds play an important role in medicinal chemistry, where they are responsible for up to 15% of the pharmaceutical products oil the market, While natural products are Valuable sources of new chemical entities, natural fluorinated Molecules are extremely rare and the pharmaceutical industry has not benefited from a microbial source of this class of compounds. Streptomyces cattleya is all unusual bacterium in that it elaborates fluoroacetate and the amino acid 4-fluorothreonine. The discovery in 2002 of the fluorination enzyme FIA responsible for C-F bond formation in S. cattleya. and its subsequent characterization, opened Lit) for the first time the prospect Of genetically engineering fluorometabolite production front fluoride ion in host organisms. As a proof of principle, we report here the induced production of fluorosalinosporamide by replacing the chlorinase gene salL from Solinispora tropica with the fluorinase gene flA.

Original languageEnglish
Pages (from-to)378-382
Number of pages5
JournalJournal of Natural Products
Volume73
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • INHIBITORS
  • ANTIPROTEALIDE
  • STREPTOMYCES-CATTLEYA
  • MECHANISM
  • BIOSYNTHESIS
  • NATURAL-PRODUCT
  • CHLORINASE
  • PROTEASOME
  • HALOGENATION
  • SALINOSPORAMIDE-A

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