Monitoring of submerged cultures of Streptomyces clavuligerus strains for metabolic flux distribution analysis

• Grant number: 12/22181-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2013
• End date: January 31, 2015
• Field of knowledge: Engineering - Chemical Engineering - Chemical Technology
• Principal Investigator: Maria Lucia Gonsales da Costa Araujo
• Grantee: Amanda Salvador Baptista
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Streptomyces clavuligerus produces various secondary metabolites of therapeutic interest: clavulanic acid, a potent inhibitor of beta-lactamases, and twenty other clavams, several of them with antifungal activity; cephamycin C, a beta-lactam antibiotic used to produce several semi synthetic antibiotics with action against anaerobic bacteria; tunicamycin, a mixture of homologous nucleoside that inhibit the glycosylation of proteins in prokaryotes and eukaryotes; holomycin, a dithiolopyrrolone with bacteriostatic and cytotoxic activities in mammals. Obtaining any of these metabolites in larger quantities depends on genetic and environmental factors that govern how the primary and secondary metabolisms compete for key-compounds. In this project, it will be investigate metabolic differences between two S. clavuligerus strains, the wild type ATCC 27064 and a mutant that not produces clavulanic acid and produces higher titers of holomycin than the wild strain. The mutant resulted from using classical mutagenesis of the wild type strain with methyl methanesulfonate followed by successive subcultures and submerged cultures, and screening processes. In vivo data of the submerged cultures will be use to the metabolic flux distribution analysis with the aid of a computer program designed for this purpose.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LEITE, CARLA A.; CAVALLIERI, ANDRE P.; BAPTISTA, AMANDA S.; ARAUJO, MARIA L. G. C.. Dissociation of cephamycin C and clavulanic acid biosynthesis by 1,3-diaminopropane in Streptomyces clavuligerus. FEMS Microbiology Letters, v. 363, n. 1, JAN 2016. (12/22181-4, 13/02632-4, 05/55079-4)

CAVALLIERI, ANDRE PASTRELO; BAPTISTA, AMANDA SALVADOR; LEITE, CARLA ANDREA; GONSALES DA COSTA ARAUJO, MARIA LUCIA. A case study in flux balance analysis: Lysine, a cephamycin C precursor, can also increase clavulanic acid production. Biochemical Engineering Journal, v. 112, p. 42-53, AUG 15 2016. (12/22181-4, 13/02632-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BAPTISTA, Amanda Salvador. Monitoramento de cultivos submersos de linhagens de Streptomyces clavuligerus para a quantificação de distribuição de fluxos metabólicos. 2015. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Química. Araraquara Araraquara.