Characterization of two 2-isopropylmalate synthase homologs from Thermus thermophilus HB27

Biochem Biophys Res Commun. 2018 Jun 22;501(2):465-470. doi: 10.1016/j.bbrc.2018.05.013. Epub 2018 May 10.

Abstract

2-Isopropylmalate synthase (IPMS) catalyzes the first step of leucine biosynthesis and is regulated via feedback inhibition by leucine. The thermophilic bacterium, Thermus thermophilus HB27, has two IPMS homologous genes: TTC0847 and TTC0849, both of which are in the branched-chain amino acid biosynthetic gene cluster. Since enzymes involved in the leucine biosynthetic pathway are evolutionarily related to those in isoleucine biosynthesis, TTC0847 and TTC0849 are expected to function as IPMS or citramalate synthase, which is the first enzyme in the isoleucine biosynthetic pathway from pyruvate. We characterized these proteins in vitro and in vivo, and revealed that TTC0849 plays a key role in the biosynthesis of leucine and isoleucine, whereas TTC0847 is only involved in that of isoleucine.

Keywords: 2-Isopropylmalate synthase; BCAA biosynthesis; Citramalate synthase; Thermus thermophilus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Isopropylmalate Synthase / chemistry
  • 2-Isopropylmalate Synthase / genetics
  • 2-Isopropylmalate Synthase / metabolism*
  • Amino Acid Sequence
  • Biosynthetic Pathways
  • Catalytic Domain
  • Gene Deletion
  • Isoleucine / metabolism
  • Leucine / metabolism
  • Models, Molecular
  • Multigene Family
  • Sequence Alignment
  • Thermus thermophilus / chemistry
  • Thermus thermophilus / enzymology*
  • Thermus thermophilus / genetics
  • Thermus thermophilus / metabolism

Substances

  • Isoleucine
  • 2-Isopropylmalate Synthase
  • Leucine