title: Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus.
abstract: This paper reports a novel use of cluster analysis for the identification of intermediary metabolites that are produced at rates closely correlated with those of antibiotic biosynthesis. This information was used to devise culture feeds resulting in enhanced production of clavulanic acid, an antibiotic of current worldwide commercial interest. The feeding strategies apparently alleviated a rate-limiting supply of the C3 precursor of clavulanic acid. C3 limitation may be a consequence of unusual nitrogen and carbon metabolism in Streptomyces clavuligerus. This approach has potential as a generic method for influencing biosynthetic pathway fluxes using feeds without knowledge of the biosynthetic pathway.
authors.affiliation: Microbial Physiology and Ecology Group, University of Surrey, Guildford, Surrey GU2 5XH, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Ives
authors.affiliation: Microbial Physiology and Ecology Group, University of Surrey, Guildford, Surrey GU2 5XH, UK.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Bushell
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000643:Ammonium Chloride; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D019149:Bioreactors; D019818:Clavulanic Acid / Q000096:biosynthesis*; D016000:Cluster Analysis; D003470:Culture Media; D008956:Models, Chemical; D013302:Streptomyces / Q000254:growth & development / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D003470:Culture Media; D000643:Ammonium Chloride; D019818:Clavulanic Acid