Investigation of the function and requirement of two halogenases from the glycopeptide A47934 biosynthetic gene cluster

• Grant number: 14/15510-7
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: November 01, 2014
• End date: April 30, 2015
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Marcio Vinicius Bertacine Dias
• Grantee: Tábata Peres Cardoso
• Supervisor: Andrew William Truman
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Institution abroad: John Innes Centre, England
• Associated to the scholarship: 12/23427-7 - Structural analysis of halogenases identified in biosynthetic gene clusters of glycopeptide antibiotics., BP.MS

Abstract

Organohalogen natural products represent an important role in the research of natural products. Various experiments have shown that natural compounds may have their biologic activity altered by presence of absence of halogen. Glycopeptide antibiotics, such as vancomycin and teicoplanin are halogenated natural products and they have substantial medical importance. They are clinically used in the treatment of gram-positive infections, mainly against Staphylococcus aureus, including methicillin resistant strains. It has been proved that the absence of a single chloride substituent in the vancomycin molecule (dechlorovancomycin) causes a reduction of more than 70% of its activity. This observation shows the importance of the chloride atoms for the activity of glycopeptide antibiotics. However, the halogenases, which are the enzymes responsible to catalyse the attachment of halogens in natural products, are not well understood and there are only a few recent studies about the halogenases from glycopeptide biosynthesis. In this project, we intend to study two different halogenases identified in gene cluster of compound A47934 from Streptomyces toyocaensis at the laboratory of Dr. Andrew Truman in the John Innes Centre (Norwich, UK), an international centre of excellence in plant science and microbiology. We intend to apply methods of Streptomyces genetics and combinatorial biosynthesis to understand the function of these halogenases and also attempt to produce new derivatives of glycopeptides with different halogenation patterns using gene deletions and complementation with exogenous genes. (AU)