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Production of new bioactive compounds by plants and bacteria using new and improved halogenases

Reference	BBS/E/J/000CA554
Principal Investigator / Supervisor	Professor Sarah O'Connor
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	65,217
Status	Completed
Type	Institute Project
Start date	01/08/2014
End date	31/03/2017
Duration	31 months

Abstract

Natural products produced by plants and microorganisms exhibit a wealth of agriculturally and medicinally significant activities. Over the past three decades more than 60% of anticancer agents and over 70% of antibiotics entering clinical trials were based on natural products. The introduction of a halogen into a natural product has frequently been demonstrated to improve bioactivity and bioavailability. Furthermore, the incorporation of chlorine or bromine into a natural product provides a reactive handle that may be utilised for further site-specific functionalisation. The inherent complexity of many natural products renders them and their analogues hard to access synthetically. A more expeditious approach is to harness the processes that generate them. Using flavin-dependent halogenases regioselective incorporation of halogen atoms (chloride and bromide) can be achieved. Flavin-dependent halogenases are two-component systems consisting of a flavin reductase producing FADH2 and the halogenase. The halogenase does not require a specific flavin reductase enabling the convenient possibility of using flavin reductases from different bacteria at will. The genes of flavin-dependent halogenases accepting different substrates have been cloned, over-expressed, and some of the enzymes were characterised. Using such enzymes, members of this consortium have demonstrated the suitability of tryptophan halogenases to modify biosynthetic pathways in bacteria and plants to obtain new compounds and showed that it is possible to modify the regioselectivity and substrate specificity of these enzymes. These results underpin the success of the proposed project.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Industrial Biotechnology, Microbiology, Plant Science, Synthetic Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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