Gene expression enabling synthetic diversification of natural products: chemogenetic generation of pacidamycin analogs.
Introduction of prnA, the halogenase gene from pyrrolnitrin biosynthesis, into Streptomyces coeruleorubidus resulted in efficient in situ chlorination of the uridyl peptide antibotic pacidamycin. The installed chlorine provided a selectably functionalizable handle enabling synthetic modification of the natural product using mild cross-coupling conditions in crude aqueous extracts of the culture broth.
Deb Roy
Abhijeet
A
School of Chemistry, University of East Anglia, Norwich NR4 7TJ, UK.
Grüschow
Sabine
S
Cairns
Nickiwe
N
Goss
Rebecca J M
RJ
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001685:Biological Factors / Q000096:biosynthesis* / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D015394:Molecular Structure; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D011741:Pyrimidine Nucleosides / Q000096:biosynthesis* / Q000737:chemistry
D000900:Anti-Bacterial Agents; D001685:Biological Factors; D011741:Pyrimidine Nucleosides; D010088:Oxidoreductases; C407363:tryptophan halogenase