Characterization of a broad-range disulfide reductase from Streptomyces clavuligerus and its possible role in beta-lactam antibiotic biosynthesis

We show here that S. clavuligerus possesses an NADPH-dependent disulfide reductase of broad substrate specificity that efficiently catalyzes the reduction of disulfide bonds in bis-ACV and in other low-molecular-weight disulfide containing compounds and proteins

Y Aharonowitz; Y Av-Gay; R Schreiber; G Cohen


Scholarcy highlights

  • Streptomyces clavuligerus is a potent producer of penicillin and cephalosporin antibiotics
  • The initial steps in the biosynthesis of these 3-lactam antibiotics involve the formation of a linear tripeptide, 5-(L-at-aminoadipyl)-L-cysteinyl-D-valine, and its subsequent conversion to isopenicillin N by the enzyme isopenicillin N synthase
  • The purpose of the present paper is to describe the characterization of a disulfide reductase from a 3-lactamproducing Streptomyces species that accepts bis-ACV as a substrate and that may play a role in the biosynthesis of penicillin
  • The biosynthesis of all penicillins and cephalosporins begins with the formation of ACV and its conversion to isopenicillin N
  • We show here that S. clavuligerus, a potent producer of f-lactam antibiotics, possesses an NADPHdependent disulfide reductase of broad substrate specificity
  • Its activity was greatest toward dithiobis(2-nitrobenzoic acid), bis-ACV, GSSG, and CoASSCoA and much lower toward disulfides of cysteine and the dipeptide cysteinyl-glycine
  • We propose that disulfide reductase may play a role in maintaining the intracellular level of reduced ACV in ,3-lactam-producing streptomycetes, thereby supporting the rate of synthesis of isopenicillin N

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