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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2016.tde-10052016-090949
Document
Author
Full name
Maria Alejandra Ferreira Torres
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Maldonado, Gabriel Padilla (President)
Baldini, Regina Lúcia
Lotufo, Leticia Veras Costa
Title in Portuguese
Análise genômica de Streptomyces olindensis DAUFPE 5622 e de suas vias crípticas para a obtenção de novos metabólicos secundários de interesse biotecnológico.
Keywords in Portuguese
Cluster biosintético
Streptomyces
Anotação de genoma
Cosmomicina D
Genome mining

Super-expressão de genes reguladores
Abstract in Portuguese
Os compostos de origem microbiana tem readquirido interesse pela biodisponibilidade, especificidade de alvo e diversidade química, mas as vias biosintéticas permanecem crípticas em condições de cultura. Uma estratégia para expressa-las é a super-expressão de genes ativadores. O laboratório de Bio-Produtos no ICB na USP tem trabalhado com Streptomyces olindensis produtor da Cosmomicina D uma molécula com atividade antitumoral de interesse devido ao padrão de glicosilação. O genoma de S. olindensis foi sequenciado e submetido ao NCBI (JJOH00000000) e utilizando o software antiSMASH foram identificados 33 clusters envolvidos na produção de metabolitos secundários. Encontraram-se clusters gênicos para a produção de metabolitos como Melanina, Geosmina, entre outros. Além, foi realizada uma analise de genômica comparativa para caracterizar e anotar as 22 vias biossintéticas desconhecidas em S. olindensis. Finalmente, escolheram-se a via do aminociclitol e um Policetídeo Tipo I para a super-expressão de genes reguladores levando a detecção do composto sob condições de cultura.
Title in English
Analysis of Streptomyces olindensis DAUFPE 5622 genome and its cryptic pathways to obtain new secondary metabolites of biotechnological interest.
Keywords in English
Streptomyces
Biosynthetic Cluster
Cosmomycin D
Genome annotation
Genome mining
Overexpression of regulator genes
Abstract in English
Microbial metabolites regain interest due to its bioavailability, target specificity and chemical diversity, but the biosynthetic pathways remain silenced under culture conditions. A strategy to obtain them is the over expression of regulatory genes. Bio-products laboratory at USP has been working with Streptomyces olindensis, products of Cosmomycin D, an antitumoral molecule with a distinctive glycosylation pattern. S. olindensis genome was sequenced and submitted to NCBI (JJOH00000000) and employing antiSMASH server 33 secondary metabolite related clusters were identified. Known pathways were found such as genes for melanin production, Geosmin and others. Additionally, a comparative genomic approach was used to characterize the 22 biosynthetic unknown pathways described in S. olindensis. Subsequently, Aminocyclitol and Polyketide Type I were chosen to evaluated, over expressing the regulatory genes, leading to the compound detection in regular culture conditions.
 
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Publishing Date
2016-05-10
 
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