P4FIFTY

Development of Cytochrome P450 Enzymes for the Chemical Manufacturing Industries

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 Obiettivo del progetto (Objective)

'The objective of the P4FIFTY project is to deliver a trans-European network of industrially oriented white biotechnologists fully trained in the application of cytochrome P450 monooxygenases (P450s) for application in the chemical manufacturing and pharmaceutical industries. This will involve academic groups investigating P450 diversity exploration from the wild type enzymes and their genes, genome mining for novel P450s, the expression of these in suitable hosts, the enzymology and molecular biological manipulation of these (including directed evolution and high throughput screening [HTS] methods), the chemical application and finally the chemical and biochemical engineering aspects of application. These inputs are supported by two industrial partners one from the pharmaceutical industries (drug metabolism and synthesis) and one from the large scale chemical manufacturing industry.'

Introduzione (Teaser)

Nature is a treasure chest of inspirational ideas among which is the application of enzymes, nature's catalysts, to biotechnology. A large training network is developing a toolbox of biocatalysts to speed synthesis of value-added chemicals.

Descrizione progetto (Article)

Selective oxidation reactions are a challenging issue in modern organic chemistry, and their achievement with biocatalysts could be one of the most industrially important transformations. These reactions require highly reactive and expensive oxygen transfer agents (catalysts) that often display poor selectivity. Nature's oxygenases such as cytochrome P450 monooxygenases have both high activity and good selectivity, leading to high-value compounds that are difficult if not impossible to produce with conventional chemical routes.

The training network supported with EU funding of the http://www.p4fifty.eu/ (P4FIFTY) (Development of cytochrome P450 enzymes for the chemical manufacturing industries) project plans to provide a step-change in the realisation of P450 potential. High reactivity and selectivity should lead to one-step synthesis of complex molecules for numerous applications in the pharmaceutical, flavours and fragrances, and fine chemicals industries.

Fellows are supervised and mentored by international experts and have access to state-of-the-art equipment. The hands-on training is complemented by a variety of courses and seminars and a strong industrial training element. Researchers have already participated in one workshop on scaling up P450 bioprocesses and another on the use of conformational and informatics tools to improve P450 biocatalytic performance. They have attended numerous international meetings and participated in outreach activities, including lectures to schoolchildren at a Summer School of Chemistry.

Research is progressing very well. The team is screening wild-type enzymes and their genes in search of novel P450s. Scientists have improved techniques for screening and expression of P450 genes and for prediction of stereoselectivity. Several libraries have been created and process models are pointing to optimisation of strategies.

P450s can catalyse a wide variety of industrially relevant reactions and do so better, cheaper and without harsh chemicals compared to conventional chemical routes. P4FIFTY is well on its way to delivery of a toolbox of well-characterised and stable whole-cell P450 biocatalysts and a searchable database with a description of their use to synthesise specific products. This should stimulate new applications and the development of new processes, strengthening the EU economy in a field of growing importance.