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Tailoring Enzymes for Natural Product Synthesis

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Enzymes produce antifungal agents

Central to the biosynthesis of natural compounds are tailored enzymes that modify their structure and function. Translating knowledge from the biosynthetic pathways of natural products into organic chemistry would contribute to the in vitro production of antibiotics.

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Understanding natural product biosynthesis would help in optimisation of the production of secondary metabolites with promising biological activities. Αmbruticin and jerangolid are two antifungal compounds that are synthesised by the Sorangium cellulosum bacterium. Scientists on the EU-funded NPTAILORINGENZYMES (Tailoring enzymes for natural product synthesis) project worked to accelerate the production of these compounds in vitro using specific enzymes implicated in their biosynthetic pathways. To achieve this, they cloned the genes for all enzymes and expressed them in E. coli. Following successful purification, they developed activity assays for several key enzymes. Researchers could now fully characterise their biocatalytic potential and obtain a better understanding of the ambruticin and jerangolid biosynthesis mechanisms. The NPTAILORINGENZYMES study facilitated the direct enzymatic synthesis of oxygen heterocycles, an abundant structural element of many pharmacologically relevant natural products. In addition, it provided the necessary knowledge to improve the production of ambruticin and jerangolid. Its overall contribution towards medicinal chemistry as well as drug research is undisputed given the great valorisation potential of natural antibiotics.

Keywords

Enzyme, antifungal agents, antibiotics, ambruticin, jerangolid

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