Structure-directed construction of a high-performance version of the enzyme FabG from the photosynthetic microorganism Synechocystis sp. PCC 6803

FEBS Lett. 2015 Oct 7;589(20 Pt B):3052-7. doi: 10.1016/j.febslet.2015.09.001. Epub 2015 Sep 7.

Abstract

PhaB (acetoacetyl-CoA reductase) catalyzes the reduction of acetoacetyl-CoA to (R)-3-hydroxybutyryl-CoA in polyhydroxybutyrate (PHB) synthesis and FabG (3-ketoacyl-acyl-carrier-protein reductase) catalyzes the β-ketoacyl-ACP to yield (R)-3-hydroxyacyl-ACP in fatty acid biosynthesis. Both of them have been classified into the same group EC 1.1.1. PhaB is limited with substrate specificities, while FabG was considered as a potential PhaB due to broad substrate selectivity despite of low activity. Here, X-ray crystal structures of FabG and PhaB from the photosynthetic microorganism Synechocystis sp. PCC 6803 were resolved. Based on them, a high-performance FabG on acyl-CoA directed by structural evolution was constructed that may serve as a critical enzyme to partition carbon flow from fatty acid synthesis to PHA.

Keywords: 3-Ketoacyl-acyl-carrier-protein reductase; Acetoacetyl-CoA reductase; Polyhydroxyalkanoates; Structure; Synechocystis sp. PCC 6803.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxoacyl-(Acyl-Carrier-Protein) Reductase / chemistry
  • 3-Oxoacyl-(Acyl-Carrier-Protein) Reductase / genetics
  • 3-Oxoacyl-(Acyl-Carrier-Protein) Reductase / metabolism*
  • Acyl Carrier Protein / chemistry
  • Acyl Carrier Protein / metabolism
  • Acyl Coenzyme A / chemistry
  • Acyl Coenzyme A / metabolism
  • Alcohol Oxidoreductases / chemistry
  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism*
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Mutation
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Synechocystis / enzymology*
  • Synechocystis / genetics
  • Synechocystis / metabolism

Substances

  • Acyl Carrier Protein
  • Acyl Coenzyme A
  • Bacterial Proteins
  • acetoacetyl CoA
  • Alcohol Oxidoreductases
  • 3-Oxoacyl-(Acyl-Carrier-Protein) Reductase
  • acetoacetyl-CoA reductase