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SynPlex SIGNED

Tailored chemical complexity through evolution-inspired synthetic biology

Total Cost €

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EC-Contrib. €

0

Partnership

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 SynPlex project word cloud

Explore the words cloud of the SynPlex project. It provides you a very rough idea of what is the project "SynPlex" about.

enzymology    engineering    therapeutic    predictable    structures    evolution    unparalleled    achieves    innovative    harness    line    building    acyltransferase    interrogate    parts    evolutionary    synthases    components    exhibit    unprecedented    hybrid    provides    biosynthetic    generate    platforms    mosaic    richness    creating    metabolic    nature    extensively    incorporates    polyketide    pkss    biochemical    formed    broad    assembly    module    strategy    modular    toolbox    complexity    multidisciplinary    principles    hypothesis    microbial    block    immunosuppressive    agents    anticancer    polyketides    discovered    canonical    enzyme    biology    enzymes    phenomenon    diversity    consequence    create    faceted    bioactive    utilize    visions    tendency    engineer    molecular    feat    pks    antiinfective    fashion    combinatorial    compounds    merges    understand    metabolites    synplex    construct    chemistry    natural    proteins    true    modifies    unravel    trans    form    synthetic   

Project "SynPlex" data sheet

The following table provides information about the project.

Coordinator
EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH 

Organization address
address: Raemistrasse 101
city: ZUERICH
postcode: 8092
website: https://www.ethz.ch/de.html

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Total cost 2˙495˙755 €
 EC max contribution 2˙495˙755 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-08-01   to  2022-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH CH (ZUERICH) coordinator 2˙495˙755.00

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 Project objective

Creating true molecular complexity in a modular, combinatorial fashion is one of the great visions in applied enzymology and chemistry. Nature achieves this feat by using modular biosynthetic enzymes. These microbial proteins generate many of the most important natural products of therapeutic value, including antiinfective, anticancer, and immunosuppressive agents. To construct such compounds, each enzyme module incorporates and often modifies one building block in an assembly line-like process. Among the known modular enzymes, the recently discovered trans-acyltransferase polyketide synthases (trans-AT PKSs) exhibit an unparalleled biosynthetic diversity and tendency to form extensively mosaic-like hybrid enzymes during evolution. As a consequence, many bioactive polyketides generated by these enzymes exhibit combinatorial-like hybrid structures. This phenomenon provides unprecedented opportunities to understand the evolution of metabolic complexity and to apply these principles to metabolic engineering through parts-based synthetic biology. SynPlex will use a novel hypothesis-driven, multi-faceted strategy to interrogate and utilize the distinct combinatorial properties and metabolic richness of trans-AT PKSs. This multidisciplinary project aims to (i) unravel principles of how mosaic PKSs and their metabolites are formed in Nature, (ii) characterize non-canonical PKS components, (iii) create a toolbox of PKS parts for synthetic biology based on these evolutionary and biochemical principles, and (iv) harness the combinatorial potential of trans-AT systems to access complex natural as well as non-natural products. This innovative concept that merges evolutionary biology, enzymology, synthetic biology, and chemistry will result in a broad understanding of these most complex of all known proteins. It has the potential to provide generic, robust synthetic biology platforms to engineer complex polyketides with a wide range of features in a predictable way.

 Publications

year authors and title journal last update
List of publications.
2018 Tetsushi Mori, Jackson K. B. Cahn, Micheal C. Wilson, Roy A. Meoded, Vincent Wiebach, Ana Flávia Canovas Martinez, Eric J. N. Helfrich, Andreas Albersmeier, Daniel Wibberg, Steven Dätwyler, Ray Keren, Adi Lavy, Christian Rückert, Micha Ilan, Jörn Kalinowski, Shigeki Matsunaga, Haruko Takeyama, Jörn Piel
Single-bacterial genomics validates rich and varied specialized metabolism of uncultivated Entotheonella sponge symbionts
published pages: 1718-1723, ISSN: 0027-8424, DOI: 10.1073/pnas.1715496115
Proceedings of the National Academy of Sciences 115/8 2020-03-11
2018 Silke I. Probst, Christine Vogel, Julia A. Vorholt, Jörn Piel
Genome Mining-guided and MALDI Imaging-assisted Discovery of New Antibiotics
published pages: 816-816, ISSN: 0009-4293, DOI: 10.2533/chimia.2018.816
CHIMIA International Journal for Chemistry 72/11 2020-03-11
2019 Thomas A. Scott, Jörn Piel
The hidden enzymology of bacterial natural product biosynthesis
published pages: 404-425, ISSN: 2397-3358, DOI: 10.1038/s41570-019-0107-1
Nature Reviews Chemistry 3/7 2020-03-11
2018 Drew T. Wagner, Zhicheng Zhang, Roy A. Meoded, Alexis J. Cepeda, Jörn Piel, Adrian T. Keatinge-Clay
Structural and Functional Studies of a Pyran Synthase Domain from a trans -Acyltransferase Assembly Line
published pages: 975-983, ISSN: 1554-8929, DOI: 10.1021/acschembio.8b00049
ACS Chemical Biology 13/4 2019-06-06
2018 Reiko Ueoka, Agneya Bhushan, Silke I. Probst, Walter M. Bray, R. Scott Lokey, Roger G. Linington, Jörn Piel
Genome-Based Identification of a Plant-Associated Marine Bacterium as a Rich Natural Product Source
published pages: 14519-14523, ISSN: 1433-7851, DOI: 10.1002/anie.201805673
Angewandte Chemie International Edition 57/44 2019-06-06
2018 Reiko Ueoka, Miriam Bortfeld-Miller, Brandon I. Morinaka, Julia A. Vorholt, Jörn Piel
Toblerols: Cyclopropanol-Containing Polyketide Modulators of Antibiosis in Methylobacteria
published pages: 977-981, ISSN: 1433-7851, DOI: 10.1002/anie.201709056
Angewandte Chemie International Edition 57/4 2019-06-06
2018 Roy A. Meoded, Reiko Ueoka, Eric J. N. Helfrich, Katja Jensen, Nancy Magnus, Birgit Piechulla, Jörn Piel
A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones
published pages: 11644-11648, ISSN: 1433-7851, DOI: 10.1002/anie.201805363
Angewandte Chemie International Edition 57/36 2019-06-06
2018 Brandon I. Morinaka, Edgars Lakis, Marjan Verest, Maximilian J. Helf, Thibault Scalvenzi, Anna L. Vagstad, James Sims, Shinichi Sunagawa, Muriel Gugger, Jörn Piel
Natural noncanonical protein splicing yields products with diverse β-amino acid residues
published pages: 779-782, ISSN: 0036-8075, DOI: 10.1126/science.aao0157
Science 359/6377 2019-06-06
2018 Eric J. N. Helfrich, Christine M. Vogel, Reiko Ueoka, Martin Schäfer, Florian Ryffel, Daniel B. Müller, Silke Probst, Markus Kreuzer, Jörn Piel, Julia A. Vorholt
Bipartite interactions, antibiotic production and biosynthetic potential of the Arabidopsis leaf microbiome
published pages: 909-919, ISSN: 2058-5276, DOI: 10.1038/s41564-018-0200-0
Nature Microbiology 3/8 2019-06-06

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