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SynPlex SIGNED

Tailored chemical complexity through evolution-inspired synthetic biology

Total Cost €

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EC-Contrib. €

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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.

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

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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