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Mining Streptomyces sp. B1 metabolites: isolation and characterization

Grant number: 16/25735-1
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): April 01, 2017
Effective date (End): March 31, 2018
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:Luciana Gonzaga de Oliveira
Grantee:Renata Sigrist
Supervisor: Bradley S. Moore
Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: University of California, San Diego (UC San Diego), United States  
Associated to the scholarship:15/01013-4 - Mining a t1PKS-transAT PKS-NRPS in Streptomyces sp. genome, BP.DD


Actinobacteria are a phylum of gram-positive terrestrial or aquatic bacteria of significant importance for pharmaceutical industry and academic research due to their great potential to biosynthesize different types of natural products, including antibiotics and anticancer agents. Streptomyces is the largest bacterial genera from this phylum and several sequenced genomes have revealed an abundance of gene clusters codifying for enzymes from secondary metabolism demonstrating an underestimated potential to produce important bioactive metabolites. Among the most useful natural products, those biosynthesized by nonribosomal peptides synthetases and polyketide synthases share both high molecular complexity and therapeutic activity. A hybrid NRPS - type I PKS gene cluster encoding the biosynthesis of a potential unknown metabolite was annotated from the whole genome sequencing of the endophytic strain Streptomyces sp. B1 isolated from Citrus ssp. In this internship project, complementing the current PhD project (2015/01013-4), we propose to perform transcriptional analysis by real-time quantitative PCR (qPCR) of the biosynthetic gene cluster in order to decipher the metabolite produced by the action of t1PKS-transATPKS-NRPS. Additionally, as a complementary approach of the recombination methodologies already explored we intend to apply transformation-associated recombinantion (TAR) direct cloning to promote the heterologous expression of an entire gene cluster in S. coelicolor host. (AU)

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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)
LUHAVAYA, HANNA; SIGRIST, RENATA; CHEKAN, JONATHAN R.; MCKINNIE, SHAUN M. K.; MOORE, BRADLEY S.. Biosynthesis of l-4-Chlorokynurenine, an Antidepressant Prodrug and a Non-Proteinogenic Amino Acid Found in Lipopeptide Antibiotics. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, v. 58, n. 25, p. 8394-8399, . (16/25735-1)
SIGRIST, RENATA; LUHAVAYA, HANNA; MCKINNIE, SHAUN M. K.; DA SILVA, AMANDA FERREIRA; JURBERG, IGOR D.; MOORE, BRADLEY S.; DE OLIVEIRA, LUCIANA GONZAGA. Nonlinear Biosynthetic Assembly of Alpiniamide by a Hybrid cis/trans-AT PKS-NRPS. ACS Chemical Biology, v. 15, n. 4, p. 1067-1077, . (19/10564-5, 17/24017-0, 14/50249-8, 16/25735-1, 14/12727-5, 15/01013-4)

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