SMs-Gut · Functional characterization of specialized metabolites from gut microbiomes
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-11-01 → 2022-10-31
- EU contribution
- €174,806
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Functional characterization of specialized metabolites from gut microbiomes
Gut-related diseases, such as CRC and IBC, pose significant health threats to mankind. Yet the mechanisms for their development and progression are still not well understood. In particular, the potential role of the gut microbiota and their specialized metabolism in this context is fully unclear. Understanding the impact of the interaction of gut microbiota and host in the context of disease is crucial to develop better preventive measures and treatment options and thus has the potential to help solve important medical questions. Within this project, novel methods for the targeted discovery, production, and functional study of specialized gut metabolism have been developed. These tools are important to enable future systematic studies on gut health and disease.
Data: CORDIS, © European Union
Project objective
Composition changes of the human gut microbiome has been associated with a series of diseases. However, little is known about the mechanism of this microbiome alteration. Recent in silico studies revealed thousands of biosynthetic gene clusters (BGCs) that encode diverse types of specialized metabolites from human microbiomes. Many of these molecules are potentially involved in shaping microbiome structure or directly affect host cell and contribute to disease development. To date, only colibactin, a hybrid polyketide/non-ribosomal peptide produced by Escherichia coli in human gut, has been experimentally validated for its deleterious metabolic impact on human host and linked to the development of colorectal cancer (CRC). Thus, this project aims to expand the knowledge of specialized metabolites produced by gut microbiome and unravel their role in development of inflammatory bowel disease (IBD) and CRC. State-of-the-art bioinformatic, synthetic biology and chemical-analytic technologies will be used to tackle this challenge. In silico identification of BGCs will be facilitated by sequence homology search and the occurrence of function-related resistant makers. The cloning process will be realized by either capturing native BGCs, adopting polymerase amplification or using synthetic DNA, followed by HiFi DNA assembly, Red/ET recombineering based DNA integration method or combining of both strategies. The chemical diversity of these specialized metabolites will be unlocked by heterologous expression of the cloned BGCs and structure elucidation of the produced molecules. The biological functions of the discovered compounds will be established by probing their genotoxicity and cytotoxicity in vitro with human intestinal cell lines.
Original text from CORDIS.
Participants
- TECHNISCHE UNIVERSITAET DRESDEN · DresdenCoordinatorGermany
Links
Data: CORDIS, © European Union