title: Clavulanic acid production by the MMS 150 mutant obtained from wild type Streptomyces clavuligerus ATCC 27064.
abstract: Clavulanic acid (CA) is a powerful inhibitor of the beta-lactamases, enzymes produced by bacteria resistants to penicillin and cefalosporin. This molecule is produced industrially by strains of Streptomyces clavuligerus in complex media which carbon and nitrogen resources are supplied by inexpensive compounds still providing high productivity. The genetic production improvement using physical and chemical mutagenic agents is an important strategy in programs of industrial production development of bioactive metabolites. However, parental strains are susceptible to loss of their original productivity due genetic instability phenomenona. In this work, some S. clavuligerus mutant strains obtained by treatment with UV light and with MMS are compared with the wild type (Streptomyces clavuligerus ATCC 27064). The results indicated that the random mutations originated some strains with different phenotypes, most divergent demonstrated by the mutants strains named AC116, MMS 150 and MMS 54, that exhibited lack of pigmentation in their mature spores. Also, the strain MMS 150 presented a larger production of CA when cultivated in semi-synthetics media. Using other media, the wild type strain obtained a larger CA production. Besides, using the modifed complex media the MMS 150 strain showed changes in its lipolitic activity and a larger production of CA. The studies also allowed finding the best conditions for a lipase activity exhibited by wild type S. clavuligerus and the MMS150 mutant.
authors.affiliation: Departamento de Engenharia Química, Universidade Federal de São Carlos, São Carlos SP, Brazil.
authors.forename: Eliton
authors.initials: E
authors.lastname: da Silva Vasconcelos
authors.affiliation: Departamento de Engenharia Química, Universidade Federal de São Carlos, São Carlos SP, Brazil.
authors.forename: Vanderlei Aparecido
authors.initials: VA
authors.lastname: de Lima
authors.affiliation: Departamento de Engenharia Química, Universidade Federal de São Carlos, São Carlos SP, Brazil. ; Grupo de Biofísica Molecular "Sérgio Mascarenhas", Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
authors.forename: Leandro Seiji
authors.initials: LS
authors.lastname: Goto
authors.affiliation: Departamento de Engenharia Química, Universidade Federal de São Carlos, São Carlos SP, Brazil.
authors.forename: Isara Lourdes
authors.initials: IL
authors.lastname: Cruz-Hernández
authors.affiliation: Departamento de Engenharia Química, Universidade Federal de São Carlos, São Carlos SP, Brazil.
authors.forename: Carlos Osamu
authors.initials: CO
authors.lastname: Hokka
mesh_terms: D019818:Clavulanic Acid / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D008049:Lipase / Q000378:metabolism; D060847:Metabolic Engineering; D008741:Methyl Methanesulfonate; D016296:Mutagenesis; D009154:Mutation; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D003470:Culture Media; D019818:Clavulanic Acid; D008741:Methyl Methanesulfonate; D008049:Lipase
keywords: Streptomyces clavuligerus; clavulanic acid; lipase; mutation