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Gramibactin - A Novel Bifunctional Siderophore-NO-Donor for application in agriculture

Reference Number TO 10-00106

Challenge

Iron is a crucial element for a broad range of biochemical reactions and although abundant in the environment it is not bioavailable under aerobic conditions. Therefore, microorganisms and plants sequester siderophores - multidentate iron(III)-binding molecules - to ensure sufficient supply. In plants iron is essential for plant growth and thus correlates with high crop yields. Root-associated bacteria may serve the host plant in providing solubilized iron, thus supporting growth and fitness of the plants. In order to improve plant growth, stress tolerance and/or crop yields a continued need exists for novel means that effectively provide soluble iron to plants.

Gramibactin: the unusual N-nitroso-hydroxylamine (diazeniumdiolate) ligands efficiently bind iron and serve as nitric oxide (NO) donors.
Gramibactin: the unusual N-nitroso-hydroxylamine (diazeniumdiolate) ligands efficiently bind iron and serve as nitric oxide (NO) donors.

Technology

Disclosed is the recently discovered peptide siderophore Gramibactin, which is produced by the rhizophere bacterium Burkholderia graminis. Gramibactin features a rare N‑nitroso-hyroxylamine moiety as a novel binding motif for iron complexation. Unlike any known siderophores the iron-binding ligands have a second function as nitric oxide (NO) donor. NO is an important plant hormone involved in several regulation processes in plants. Generally synthetic NO-donors are known to promote plants fitness, root growth and tolerance towards stress. By combining these two features the novel bifunctional siderophore-NO-donor Gramibactin may serve as a natural enhancer for crop plant fitness and yield.

Commercial Opportunity

Gramibactin is offered for licensing and/or co-development.

Developmental Status

Data from PET-CT tracer studies and supplementation experiments show that maize plants take up iron from the complex, which results in a marked increase (by 50%) in chlorophyll production. In vitro assays and in vivo fluorescence imaging illustrate that gramibactin liberates NO.

Patent Situation

A European priority application has been filed in December, 2017 (EP17207667).

Further Reading

Nat. Chem. Biol. 2018 Jul 30. doi: 10.1038/s41589-018-0101-9. [Epub ahead of print]