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Science 3 May 1991:
Vol. 252. no. 5006, pp. 675 - 679
DOI: 10.1126/science.2024119
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Articles

Science, Vol 252, Issue 5006, 675-679
Copyright © 1991 by American Association for the Advancement of Science

articles

Modular organization of genes required for complex polyketide biosynthesis

S Donadio, MJ Staver, JB McAlpine, SJ Swanson, and L Katz

Department of Corporate Molecular Biology, Abbott Laboratories, Abbott Park, IL 60064.

In Saccharopolyspora erythraea, the genes that govern synthesis of the polyketide portion of the macrolide antibiotic erythromycin are organized in six repeated units that encode fatty acid synthase (FAS)-like activities. Each repeated unit is designated a module, and two modules are contained in a single open reading frame. A model for the synthesis of this complex polyketide is proposed, where each module encodes a functional synthase unit and each synthase unit participates specifically in one of the six FAS-like elongation steps required for formation of the polyketide. In addition, genetic organization and biochemical order of events appear to be colinear. Evidence for the model is provided by construction of a selected mutant and by isolation of a polyketide of predicted structure.


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A. K. Azad, T. D. Sirakova, N. D. Fernandes, and P. E. Kolattukudy (1997)
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Attack as the Best Form of Defense: Natural Products in the Forefront of Contemporary Drug Research.
M. Moore (1996)
J Biomol Screen 1, 19-21
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Repositioning of a domain in a modular polyketide synthase to promote specific chain cleavage.
J Cortes, K. Wiesmann, G. Roberts, M. Brown, J Staunton, and P. Leadlay (1995)
Science 268, 1487-1489
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The Escherichia coli Malonyl-CoA:Acyl Carrier Protein Transacylase at 1.5-Å Resolution.
L. Serre, E. C. Verbree, Z. Dauter, A. R. Stuitje, and Z. S. Derewenda (1995)
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D. Cane (1994)
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Stereospecific acyl transfers on the erythromycin-producing polyketide synthase.
A. Marsden, P Caffrey, J. Aparicio, M. Loughran, J Staunton, and P. Leadlay (1994)
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Engineered biosynthesis of novel polyketides.
R McDaniel, S Ebert-Khosla, D. Hopwood, and C Khosla (1993)
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