Production of branched-chain alkylprodiginines in S. coelicolor by replacement of the 3-ketoacyl ACP synthase III initiation enzyme, RedP

Sangjoon Mo, Beom Seok Kim, Kevin A. Reynolds

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The enzyme RedP is thought to initiate the biosynthesis of the undecylpyrolle component of the antibiotic undecylprodiginine produced by Streptomyces coelicolor. RedP has homology to FabH, which initiates fatty acid biosynthesis by condensing the appropriate acyl-CoA starter unit with malonyl ACP. We have generated a redP-deletion mutant of S. coelicolor M511 (SJM1) and shown that it produces reduced levels of prodiginines and two new analogs, methylundecylprodiginine and methyldodecylprodiginine. Incorporation studies with perdeuterated valine were consistent with these being generated using methylbutyryl-CoA and isobutyryl-CoA as starter units, respectively. Plasmid-based expression of a streptomycete fabH in the SJM1 mutant led to restoration of overall prodiginine titers but the same overall ratio of undecylprodiginines and novel prodiginines. Thus, the redP FabH can be replaced by FabH enzymes with different substrate specificities and provides a method for generating novel prodiginines.

Original languageEnglish
Pages (from-to)191-200
Number of pages10
JournalChemistry and Biology
Volume12
Issue number2
DOIs
Publication statusPublished - 2005 Feb 1
Externally publishedYes

Fingerprint

Streptomyces coelicolor
Starters
Biosynthesis
Enzymes
Acyl Coenzyme A
Valine
Coenzyme A
Substrate Specificity
Restoration
Plasmids
Fatty Acids
Anti-Bacterial Agents
prodiginine
3-ketoacyl-acyl carrier protein synthase III
Substrates
undecylprodiginine
isobutyryl-coenzyme A

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Production of branched-chain alkylprodiginines in S. coelicolor by replacement of the 3-ketoacyl ACP synthase III initiation enzyme, RedP. / Mo, Sangjoon; Kim, Beom Seok; Reynolds, Kevin A.

In: Chemistry and Biology, Vol. 12, No. 2, 01.02.2005, p. 191-200.

Research output: Contribution to journalArticle

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