Diversity in natural product families is governed by more than enzyme promiscuity alone: establishing control of the pacidamycin portfolio

Sabine Grueschow, Emma J. Rackham, Rebecca J. M. Goss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

As with many other antibiotics, pacidamycins are produced as a suite of related compounds. Unlike most other secondary metabolites, however, this diversity is not solely the result of the substrate promiscuity of the biosynthetic enzymes but also arises from a gene duplication event (Pac21, Pac21h) and control of the precursor pool (PhhA). We are demonstrating the ability to harness these three levels of control in order to direct the selective production of specific members of this family of metabolites in a "dial-a-molecule" fashion. Furthermore, PhhA is shown to be a phenylalanine 3-hydroxylase, the first of the iron- and tetrahydropterin-dependent aromatic amino acid hydroxylases to be characterised with this regioselectivity.

Original languageEnglish
Pages (from-to)2182-2186
Number of pages5
JournalChemical Science
Volume2
Issue number11
Early online date11 Aug 2011
DOIs
Publication statusPublished - 2011

Keywords

  • MECHANISM
  • SERIES
  • IDENTIFICATION
  • PSEUDOMONAS-AERUGINOSA ACTIVITY
  • PHENYLALANINE-HYDROXYLASE
  • PEPTIDYL NUCLEOSIDE ANTIBIOTICS
  • EXPRESSION
  • DOMAIN
  • BIOSYNTHETIC GENE-CLUSTER

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