Enzymatic synthesis of beta-lactam antibiotics via direct condensation

R.V. Ulijn, L. De Martin, P.J. Halling, B.D. Moore, A.E.M. Janssen

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

In this paper, the feasibility of precipitation driven synthesis of acidic and zwitterionic beta-lactam antibiotics is studied. As an example of the first type, penicillin G was produced in good yield (160 mmol kg(-1)) directly from the free acid and an-tine aqueous substrate suspension, where the synthesis product precipitated. Such a precipitation driven synthesis via direct reversal of the hydrolytic reaction is thermodynamically unfavourable for zwitterionic beta-lactam antibiotics, such as amoxicillin. In this paper, a novel method is suggested to help favour precipitation of (poorly soluble) product salts by deliberate addition of certain counter-ions. After screening a number of different counter-ions, it was found that the amoxicillin anion forms a poorly soluble salt with Zn2+. Despite increased beta-lactam degradation due to the presence of zinc ions, in a synthetic reaction with 0.1 M ZnSO4 present the synthetic yield could be increased at least 30-fold.
Original languageEnglish
Pages (from-to)215-222
Number of pages7
JournalJournal of Biotechnology
Volume99
Issue number3
DOIs
Publication statusPublished - 13 Nov 2002

Keywords

  • beta-lactam antibiotics
  • peptides
  • product precipitation
  • biocatalysis
  • solid-to-solid thermodynamically controlled synthesis
  • protease-catalyzed synthesis
  • solid peptide-synthesis
  • penicillin acylase
  • mixtures
  • equilibrium
  • dipeptides
  • conversion
  • kinetics

Fingerprint Dive into the research topics of 'Enzymatic synthesis of beta-lactam antibiotics via direct condensation'. Together they form a unique fingerprint.

  • Cite this