4A10

Apo-structure of 2-octenoyl-CoA carboxylase reductase CinF from streptomyces sp.

Summary for 4A10

• Entry DOI: 10.2210/pdb4a10/pdb
• Related: 4A0S
• Descriptor: OCTENOYL-COA REDUCTASE/CARBOXYLASE (2 entities in total)
• Functional Keywords: oxidoreductase, ccr, pks building blocks, rossmann fold
• Biological source: STREPTOMYCES SP.
• Total number of polymer chains: 4
• Total formula weight: 192122.08

Authors

Quade, N.,Huo, L.,Rachid, S.,Heinz, D.W.,Muller, R. (deposition date: 2011-09-13, release date: 2011-12-07, Last modification date: 2023-12-20)

Primary citation

Quade, N.,Huo, L.,Rachid, S.,Heinz, D.W.,Muller, R.
Unusual Carbon Fixation Giving Rise to Diverse Polyketide Extender Units
Nat.Chem.Biol., 8:117-, 2011

PubMed Abstract: 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.

PubMed: 22138621
DOI: 10.1038/NCHEMBIO.734

Experimental method

X-RAY DIFFRACTION (2.25 Å)