Abstract
Ethylene is an important phytohormone that promotes the ripening of fruits and senescence of flowers thereby reducing their shelf lives. Specific ethylene biosynthesis inhibitors would help to decrease postharvest loss. Here, we identify pyrazinamide (PZA), a clinical drug used to treat tuberculosis, as an inhibitor of ethylene biosynthesis in Arabidopsis thaliana, using a chemical genetics approach. PZA is converted to pyrazinecarboxylic acid (POA) in plant cells, suppressing the activity of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO), the enzyme catalysing the final step of ethylene formation. The crystal structures of Arabidopsis ACO2 in complex with POA or 2-Picolinic Acid (2-PA), a POA-related compound, reveal that POA/2-PA bind at the active site of ACO, preventing the enzyme from interacting with its natural substrates. Our work suggests that PZA and its derivatives may be promising regulators of plant metabolism, in particular ethylene biosynthesis.
Highlights
Ethylene is an important phytohormone that promotes the ripening of fruits and senescence of flowers thereby reducing their shelf lives
To isolate inhibitors of ethylene biosynthesis and signalling, we screened a chemical library (SP 2000, http://www.msdiscovery.com) for suppressors of the constitutive ethylene response phenotype observed in the mutants of eto[1,2] and ctr1-1. eto[1,2] is an ethylene biosynthesis mutant that shows enhanced ACC synthase (ACS) protein stability[37], whereas ctr[1] is a signalling mutant that shows constitutively activated ethylene response[38]
Further studies revealed that PZA can be converted to pyrazinecarboxylic acid (POA) in Arabidopsis cells, which is the active form of PZA to inhibit ethylene biosynthesis
Summary
Ethylene is an important phytohormone that promotes the ripening of fruits and senescence of flowers thereby reducing their shelf lives. PZA is converted to pyrazinecarboxylic acid (POA) in plant cells, suppressing the activity of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO), the enzyme catalysing the final step of ethylene formation. ACS is generally considered as the rate-limiting step in ethylene biosynthesis, there is growing evidence that ACO acts as a control point under specific developmental and stress conditions in various plant species[5,6,7]. ACO enzyme is a 2OG-oxygenase ‘related’ enzyme that belongs to the cupin superfamily, which uses a non-heme ferrous iron (Fe2 þ ) as a cofactor and facilitates the integration of molecular oxygen into a myriad of biomolecules Members of this superfamily feature a highly conserved Fe2 þ -binding motif consisting of two histidines and an acidic residue (Glu/Asp), known as the ‘facial triad’[8,9,10]. The reactive Fe is reduced by ascorbate to regenerate the catalytically active Fe2 þ
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.