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. 1993 Aug 1;90(15):7119–7123. doi: 10.1073/pnas.90.15.7119

An erythromycin analog produced by reprogramming of polyketide synthesis.

S Donadio 1, J B McAlpine 1, P J Sheldon 1, M Jackson 1, L Katz 1
PMCID: PMC47087  PMID: 8346223

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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