Use of microbial enzyme and cell preparations to synthesise oligopeptide antibiotics

Abstract

AbstractMicrobial enzymes and cells (in free or immobilised form) have so far been applied mainly in hydrolysis and bioconversion reactions, but recently there has been an increasing interest in the use of such ‘controlled catalytic biomass’ to produce fermentation products and to apply the principle to organic synthesis. Particular attention is given here to the use of immobilised enzymes and cells for producing known or new peptide antibiotics. An evaluation is presented of the applicability of this concept in the fascinating field of peptide antibiotic bioconversions and fermentations. As an important example of the use of enzymes or cells to convert peptide antibiotics into useful derivatives, free and immobilised penicillin acylases, producing the penicillin nucleus 6‐amino‐penicillanic acid, are reviewed as well as their potential to synthesise semi‐synthetic penicillins and cephalosporins. The action of acetylesterase and α‐amino acid ester hydrolase on cephalosporin compounds is also discussed. Use of enzymes and cells to synthesise antibiotics as an alternative method to conventional fermentation is subsequently reviewed. The concept of total enzymic synthesis in vitro of antibiotics is illustrated in the exploitation of the ‘multi‐enzyme thiotemplate mechanism’ of Bacillus brevis, to produce gramicidin S. Total synthesis of peptide antibiotics with immobilised living cells or mycelium as catalysts has been demonstrated recently in the cases of penicillin and bacitracin. These examples of complex multi‐step enzyme reactions might indicate the vast potential of immobilised enzyme and cell technology in fermentation, in biotechnological processes and in organic synthesis.