AL4BIOCH · Assembly Lines for Biocombinatorial Chemistry
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2019-05-01 → 2021-06-30
- Финансиране от ЕС
- 203 149 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Поликетидсинтазите (PKS) са ензимни комплекси, които изграждат сложни молекули, използвани за създаване на лекарства. Разбирането на тяхната структура помага при разработването на нови терапии и борбата с антибиотичната резистентност.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Assembly Lines for Biocombinatorial Chemistry
• What is the problem/issue being addressed? The goal of this project is to study the functional architecture of Polyketide Synthetases (PKS) and the basis for their multidomain organization and to analyse intra- and intermolecular crosstalk in substrate transfer. We aim for a fundamental understanding of the structural organization of PKS biosynthesis, which provides a basis for PKS re-engineering in drug discovery and combinatorial biosynthesis. • Why is it important for society? Because PKS and their polyketide products are of outstanding relevance for fighting disease, this project in itself holds direct translational value, and a fundamental understanding of polyketide biosynthesis is crucial for extended targeted therapeutic intervention e.g. to overcome antibiotic resistances. The combined fundamental nature and high translational potential of this project suppose strongest impact and corresponding opportunities to publish with high impact. • What are the overall objectives? The main goal of this project is to contribute to fundamental understanding of molecular mechanisms in biology and to advance the fields of chemical biology and synthetic chemistry, biochemistry and natural product research, structural biology, as well as microbiology
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Polyketide Synthases (PKS) are biological factories for the production of potent natural products, including antibiotics, anti‐cancer drugs, statins and further drugs. The exceptional chemical diversity generated by PKS is encoded in their modular architecture. The domains required for one step of precursor elongation and modification are combined into a functional polypeptide module. PKS modules can either act iteratively (iPKS) or in a linearly organized assembly line of multiple modules (modPKS). The collinearity between synthesis and protein sequence in modPKS promised the opportunity for rational re‐engineering of PKS at the genetic level in order to produce novel compounds. However, information on functional protein-protein interactions and substrate transfer in PKS beyond the level of isolated domains is sparse and divergent architectural models of module organization have been proposed. In the AL2BIOCH project, we aim to reveal the fundamental intermodular assembly line organization underlying the unique biosynthetic generation of chemical diversity by modPKS. For this purpose, we employ cryo-electron microscopy to comprehensively study the organization of modPKS bimodules as minimal representations of assembly lines organization. In combination with functional analysis, biophysical studies and chemoenzymatic trapping we address the architectures underlying directed substrate transfer. The research builds on modern and rapidly evolving techniques, including cryo electron microscopy, advanced optical imaging and biophysics, as well as chemical probes, which are most relevant for front-line molecular biology research. Success in this project will allow the host lab and organization to establish new collaborations for translating insights on modPKS architecture for the design of novel or re-engineered assembly lines for the generation of advanced chemical compounds and drug candidates.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITAT BASEL · BaselКоординаторШвейцария
Връзки
Данни: CORDIS, © Европейски съюз