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Molecular and structural bases of 1, 2 and 4 modules from the polyketide synthesis enzyme complex, DEBS, from Saccharopolyspora erythraea

Grant number: 18/10209-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2018
Effective date (End): September 30, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:Fabio Cesar Gozzo
Grantee:Valeria Scorsato
Home Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:14/17264-3 - New frontiers in structural proteomics: characterizing protein and protein complex structures by mass spectrometry, AP.TEM

Abstract

Antibiotic Resistance (AMR) poses a serious threat to public health. Brazilian National Health System (SUS) estimates that about 19,000 Brazilians dies of infections due to AMRs every year. The World Health Organization (WHO) has issued a worldwide warning on this threat and suggested the development of new antibiotics to combat these microorganisms. One approach to this problem is through structural studies of the enzymatic complexes Polyketide Synthases, the PKS. Those enzymes synthesize several natural products including antibiotics as penicillin and erythromycin. The PKS complex of the bacterium Saccharopolyspora erythraea, known as DEBS, is one of the most studied from the view of molecular and structural biology. It is responsible of the synthesis of macrolide núcleos of the antibiotic erythromycin. Although very previosly studied, little is known in relation to the modular structures and protein:protein interactions of the PKS's. To its better understanding, this project aims to characterize those enzyme complex through the use of biophysical techniques such as X-ray and SAXS crystallography; mass spectrometry such as cross-linking and hydrogen exchange by deuterium and the three-dimensional structures and interfaces of the DEBS polyketide synthase complex. The unsderstanding of DEBS modules allows future advances in the structure, function and catalysis studies of this complex for the targeted synthesis of new molecules with biological activity.