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CHLOROIRIDOIDS

Elusive enzymes with biocatalytic potential: chlorinases in the plant kingdom

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EC-Contrib. €

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Partnership

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Project "CHLOROIRIDOIDS" data sheet

The following table provides information about the project.

Coordinator
JOHN INNES CENTRE 

Organization address
address: NORWICH RESEARCH PARK COLNEY
city: NORWICH
postcode: NR4 7UH
website: www.jic.bbsrc.ac.uk

contact info
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surname: n.a.
function: n.a.
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 Coordinator Country United Kingdom [UK]
 Project website https://www.jic.ac.uk/staff/Sarah-OConnor/index.html
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2015
 Duration (year-month-day) from 2015-12-01   to  2017-11-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    JOHN INNES CENTRE UK (NORWICH) coordinator 183˙454.00

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 Project objective

A plethora of halogenated natural products documents the existence of halogenases in plants but the responsible enzymes remain elusive. Chlorinated iridoid glycosides, for instance, occur in Phlomis, a genus in the mint family. Based on knowledge of iridoid biosynthesis and a mechanistic hypothesis for the chlorination reaction, we aim to discover the underlying enzymes. We will sequence transcriptomes of Phlomis tissues in different metabolic states, identify homologs of enzymes involved in iridoid biosynthesis, and search for candidate genes showing similar expression patterns. Among these candidates, the chlorinase will be identified by assaying the reactivity of heterologously expressed protein in vitro. Biochemical and structural characterization of the chlorinase will clarify whether chlorine incorporation proceeds via a rare epoxide opening mechanism. The level of chloroiridoid production will be assessed in plants after silencing the chlorinase, in order to confirm the metabolic role of the newly discovered enzyme. Furthermore, transient expression in plants providing structurally diverse precursors will reveal whether chlorinated natural products can be made that are new to nature. The discovery of a chlorinase in higher plants will fill an important gap in our understanding of plant secondary metabolism. Given the potential of chlorine for enhancing protein-ligand interactions, such enzymes would become useful tools for biocatalysis and the engineered biosynthesis of natural products with fine-tuned medicinal properties.

 Publications

year authors and title journal last update
List of publications.
2016 Hajo Kries, Sarah E O’Connor
Biocatalysts from alkaloid producing plants
published pages: 22-30, ISSN: 1367-5931, DOI: 10.1016/j.cbpa.2015.12.006
Current Opinion in Chemical Biology 31 2019-07-24
2017 Hajo Kries, Franziska Kellner, Mohamed Omar Kamileen, Sarah E. O\'Connor
Inverted stereocontrol of iridoid synthase in snapdragon
published pages: jbc.M117.800979, ISSN: 0021-9258, DOI: 10.1074/jbc.M117.800979
Journal of Biological Chemistry 2019-07-24
2016 Hajo Kries
Biosynthetic engineering of nonribosomal peptide synthetases
published pages: 564-570, ISSN: 1075-2617, DOI: 10.1002/psc.2907
Journal of Peptide Science 22/9 2019-07-24

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