Gene Deletion Leads to Improved Valinomycin Production by Streptomyces sp. CBMAI 2042

Autor(es)

Paulo, Bruno S. ^[1] ; Sigrist, Renata ^[1] ; Angolini, Celio F. F. ^[2] ; Eberlin, Marcos N. ^[3] ; de Oliveira, Luciana G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Quim, CP 6154, BR-13083970 Campinas, SP - Brazil

^[2] Univ Fed ABC, Ctr Ciencias Nat & Humans, BR-09210580 Santo Andre, SP - Brazil

^[3] Univ Presbiteriana Mackenzie, BR-01301100 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of the Brazilian Chemical Society; v. 30, n. 3, SI, p. 673-679, MAR 2019.
• Citações Web of Science: 2

Resumo

The genus Streptomyces represents one of the largest producers of molecules with antibiotic activity. The whole genome sequencing of the endophytic microorganism Streptomyces sp. CBMAI 2042 revealed 35 gene clusters encoding for secondary metabolism including 3 non-ribosomal peptide synthetases (NRPS) and 7 NRPS-hybrids. Combining genome mining and cultivation profile analysis, the depsipeptide ionophore valinomycin was identified as one of the main metabolites produced by this strain. To better understand the metabolic machinery codified in CBMAI 2042 genome an adenylation domain from a hybrid NRPS cluster was deleted through a double crossing knockout experiment. Though the deletion was not plentiful to elucidate the encoded NRP metabolite related to the adenilation domain, an astounding increase of 10.5-fold in valinomycin production was observed in the mutant. These results suggest a metabolic flux redistribution of common substrates as an outcome of a gene target deletion. (AU)

• Processo FAPESP: 14/50249-8 - Green chemistry: sustainable synthetic methods employing benign solvents, safer reagents, and bio-renewable feedstock
• Beneficiário: Arlene Gonçalves Corrêa
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia
• Processo FAPESP: 15/01013-4 - Identificação e caracterização de uma t1PKS-transAT PKS-NRPS em Streptomyces sp. via genome mining
• Beneficiário: Renata Sigrist
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 10/51677-2 - Técnicas modernas em espectrometria de massas e desenvolvimento de novas aplicações em ciências: química, bioquímica, materiais, forense, medicina, alimentos, farmácia e veterinária
• Beneficiário: Marcos Nogueira Eberlin
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/12727-5 - Genome mining em Streptomyces
• Beneficiário: Luciana Gonzaga de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/12598-8 - Identificação de uma t1PKS-transAT PKS-NRPS em Streptomyces sp. via genome mining
• Beneficiário: Renata Sigrist
• Modalidade de apoio: Bolsas no Brasil - Mestrado