Overproduction and biochemical characterization of the Chryseobacterium meningosepticum BlaB metallo-beta-lactamase

Antimicrob Agents Chemother. 2002 Jun;46(6):1921-7. doi: 10.1128/AAC.46.6.1921-1927.2002.

Abstract

The BlaB metallo-beta-lactamase of Chryseobacterium meningosepticum CCUG4310 was overproduced in Escherichia coli by means of a T7 promoter-based expression system. The overproducing system, scaled up in a 15-liter fermentor, yielded approximately 10 mg of BlaB protein per liter, mostly released in the culture supernatant. The enzyme was purified by two ion-exchange chromatographic steps with an overall yield of 66%. Analysis of the kinetic parameters revealed efficient activities (k(cat)/K(m) ratios of >10(6) M(-1) s(-1)) toward most penam and carbapenem compounds, with the exception of the 6-alpha-methoxypenam derivative temocillin and of biapenem, which were poorer substrates. Hydrolysis of cephalosporins was overall less efficient, with a remarkable variability that was largely due to variable affinities of the BlaB enzyme for different compounds. BlaB was also able to hydrolyze serine-beta-lactamase inhibitors, including beta-iodopenicillanate, sulbactam and, although less efficiently, tazobactam.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / enzymology*
  • Bacteria / genetics
  • Binding Sites
  • Carbapenems / metabolism
  • Cephalosporins / metabolism
  • Culture Media
  • DNA, Recombinant / genetics
  • Escherichia coli / enzymology
  • Fermentation
  • Genetic Vectors
  • Kinetics
  • Penicillins / metabolism
  • Plasmids / genetics

Substances

  • Carbapenems
  • Cephalosporins
  • Culture Media
  • DNA, Recombinant
  • Penicillins