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PMID: 12811585 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Active-site residue, domain and module swaps in modular polyketide synthases.

Journal of industrial microbiology & biotechnology ·Vol. 30 ·No. 8 ·2003-08-00 ·Pages 489-94

Del Vecchio F, Petkovic H, Kendrew SG, Low L, Wilkinson B, Lill R, Cortés J, Rudd BA, Staunton J, Leadlay PF

Abstract

Sequence comparisons of multiple acyltransferase (AT) domains from modular polyketide synthases (PKSs) have highlighted a correlation between a short sequence motif and the nature of the extender unit selected. When this motif was specifically altered in the bimodular model PKS DEBS1-TE of Saccharopolyspora erythraea, the products included triketide lactones in which acetate extension units had been incorporated instead of propionate units at the predicted positions. We also describe a cassette system for convenient construction of hybrid modular PKSs based on the tylosin PKS in Streptomyces fradiae and demonstrate its use in domain and module swaps.

MeSH Terms

Anti-Bacterial Agents/biosynthesis Binding Sites Erythromycin/biosynthesis Industrial Microbiology Multienzyme Complexes/chemistry,genetics,metabolism Mutagenesis, Site-Directed Protein Structure, Tertiary Saccharopolyspora/enzymology,genetics Streptomyces/enzymology,genetics Tylosin/biosynthesis

Chemicals

Anti-Bacterial Agents Multienzyme Complexes Erythromycin Tylosin

Authors & Affiliations

10 authors, click to expand affiliations / ORCID

Del Vecchio Francesca

Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, CB2 1GA, Cambridge, UK.

Petkovic Hrvoje

Kendrew Steven G

Low Lindsey

Wilkinson Barrie

Lill Rachel

Cortés Jesús

Rudd Brian A M

Staunton Jim

Leadlay Peter F

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Article Info

Journal

Journal of industrial microbiology & biotechnology

Abbr.

J Ind Microbiol Biotechnol

ISSN

1367-5435

DOI

10.1007/s10295-003-0062-0

Published

2003-08-00

Epub

2003-00-14

Pages

489-94

Language

English

Region

Germany

NLM ID

9705544

Subset

Grants

NIAID NIH HHS · 1 R43 AI47567-01 · United States

External Links

PubMed source DOI: 10.1007/s10295-003-0062-0 View journal details

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Active-site residue, domain and module swaps in modular polyketide synthases.

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