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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Unusual carbon fixation gives rise to diverse polyketide extender units
Nature Chemical Biology, Volume 8, No. 1, Year 2012
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Description
Polyketides are structurally diverse and medically important natural products that have various biological activities. During biosynthesis, chain elongation uses activated dicarboxylic acid building blocks, and their availability therefore limits side chain variation in polyketides. Recently, the crotonyl-CoA carboxylase-reductase (CCR) class of enzymes was identified in primary metabolism and was found to be involved in extender-unit biosynthesis of polyketides. These enzymes are, in theory, capable of forming dicarboxylic acids that show any side chain from the respective unsaturated fatty acid precursor. To our knowledge, we here report the first crystal structure of a CCR, the hexylmalonyl-CoA synthase from Streptomyces sp. JS360, in complex with its substrate. Structural analysis and biochemical characterization of the enzyme, including active site mutations, are reported. Our analysis reveals how primary metabolic CCRs can evolve to produce various dicarboxylic acid building blocks, setting the stage to use CCRs for the production of unique extender units and, consequently, altered polyketides. © 2011 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Quade, Nick
Germany, Braunschweig
Helmholtz Centre for Infection Research Hzi
Huo, Liujie
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Rachid, Shwan Kamal
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Iraq, Koya
Koya University
Heinz, Dirk W.
Germany, Braunschweig
Helmholtz Centre for Infection Research Hzi
Müller, Rolf
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Statistics
Citations: 63
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1038/nchembio.734
e-ISSN:
15524469
Research Areas
Environmental
Noncommunicable Diseases