Biochemical and structural characterization of the BioZ enzyme engaged in bacterial biotin synthesis pathway

Nat Commun. 2021 Apr 6;12(1):2056. doi: 10.1038/s41467-021-22360-4.

Abstract

Biotin is an essential micro-nutrient across the three domains of life. The paradigm earlier step of biotin synthesis denotes "BioC-BioH" pathway in Escherichia coli. Here we report that BioZ bypasses the canonical route to begin biotin synthesis. In addition to its origin of Rhizobiales, protein phylogeny infers that BioZ is domesticated to gain an atypical role of β-ketoacyl-ACP synthase III. Genetic and biochemical characterization demonstrates that BioZ catalyzes the condensation of glutaryl-CoA (or ACP) with malonyl-ACP to give 5'-keto-pimeloyl ACP. This intermediate proceeds via type II fatty acid synthesis (FAS II) pathway, to initiate the formation of pimeloyl-ACP, a precursor of biotin synthesis. To further explore molecular basis of BioZ activity, we determine the crystal structure of Agrobacterium tumefaciens BioZ at 1.99 Å, of which the catalytic triad and the substrate-loading tunnel are functionally defined. In particular, we localize that three residues (S84, R147, and S287) at the distant bottom of the tunnel might neutralize the charge of free C-carboxyl group of the primer glutaryl-CoA. Taken together, this study provides molecular insights into the BioZ biotin synthesis pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Carrier Protein / metabolism
  • Acyl Coenzyme A / metabolism
  • Agrobacterium / growth & development
  • Amino Acid Sequence
  • Biocatalysis
  • Biosynthetic Pathways*
  • Biotin / biosynthesis*
  • Crystallography, X-Ray
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Molecular Docking Simulation
  • Phylogeny
  • Protein Multimerization
  • Structural Homology, Protein
  • Substrate Specificity

Substances

  • Acyl Carrier Protein
  • Acyl Coenzyme A
  • Escherichia coli Proteins
  • glutaryl-coenzyme A
  • Biotin