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Direct Pathway Cloning of Neglected Bacteria in the Hunt for Novel (Bio-)Chemistry

Objective

To overcome recent global health threats, such as antibiotic resistance, a resurgence in the discovery of new chemical and thus biomedical diversity from microbial sources is needed. Genome mining in combination with heterologous expression is an approach that will overcome these challenges. It involves incorporation of yet uncharacterized natural product genetic loci into a fast growing heterologous host. For this approach, a prolific source of novel natural product gene clusters is vital. Our collaboration with the Zentralinstitut für Ernährungs- und Lebensmittelforschung (ZIEL, Technische Universität München) provides direct access to bacterial isolates completely unexplored in regards to their potential for natural product biosynthesis. Our genome analyses have revealed that many of the ZIEL isolates harbor a large number of uncharacterized natural product gene clusters. Thus, the aim of this proposal is to heterologously express natural product gene clusters from these neglected bacteria to discover novel natural product (bio-)chemistry. Because these organisms are poorly studied, the likelihood of discovering rare or novel biochemistry is immensely increased. Here, we will utilise a novel combination of synthetic biology techniques referred to as Direct Pathway Cloning. This will enable expression vectors to be constructed by large-amplicon PCR (up to 20kb) coupled to Gibson assembly. Development of the methodology is set to revolutionise synthetic biology and metabolic engineering. Downstream outcomes of this proposal will be the identification of novel, potentially bioactive natural products, the characterisation of unusual biochemistry and the addition of enzymes to the ‘biocatalytic toolkit’ for natural product synthesis and structural alteration.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

TECHNISCHE UNIVERSITAET MUENCHEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 159 460,80
Address
Arcisstrasse 21
80333 Muenchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 159 460,80
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