Format

Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7119-23.

An erythromycin analog produced by reprogramming of polyketide synthesis.

Author information

  • 1Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064.

Abstract

The polyketide-derived macrolactone of the antibiotic erythromycin is made through successive condensation and processing of seven three-carbon units. The fourth cycle involves complete processing of the newly formed beta-keto group (beta-keto reduction, dehydration, and enoyl reduction) to yield the methylene that will appear at C-7 of the lactone ring. Synthesis of this molecule in Saccharopolyspora erythraea is determined by the three large eryA genes, organized in six modules, each governing one condensation cycle. Two amino acid substitutions were introduced in the putative NAD(P)H binding motif in the proposed enoyl reductase domain encoded by eryAII. The metabolite produced by the resulting strain was identified as delta 6,7-anhydroerythromycin C resulting from failure of enoyl reduction during the fourth cycle of synthesis of the macrolactone. This result demonstrates the involvement of at least the enoyl reductase from the fourth module in the fourth cycle and indicates that a virtually complete macrolide can be produced through reprogramming of polyketide synthesis.

PMID:
8346223
PMCID:
PMC47087
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk