CYP (cytochrome P450) biodiversity and biotechnology is of importance given the industrial applications and potential for the huge array of genes and proteins that can constitute up to 1% of a coding genome. Historical biotechnological roles for CYPs in mutant fungi diverting the flux of metabolites towards penicillin production, in biotransformations allowing the production of corticosteroids and CYPs as drug targets contribute to interest in the roles of orphan CYPs in the emerging genomes. This area includes studies related to biotransformations and bioremediation, natural product synthesis and its manipulation, tools for exploiting CYPs and using CYPs as biomarkers and drug targets. Fundamental studies on diverse structure and function, on the ecological and evolution of CYPs through geological time and in drug/pesticide resistance also contribute distinctively to this field of CYP research.

The 8th International Symposium on Cytochrome P450 Biodiversity and Biotechnology was held in Swansea, Wales on 23–27 July 2006, involving 100 international delegates and full details of the programme are available at http://www.8cypsymposium.swansea.ac.uk. The meeting reflected much of the current research that is ongoing and focused not only on xenobiotic metabolism in humans, a dominant interest in CYP (cytochrome P450) research, but on work in bacteria, lower eukaryotes, plants, insects and lower animals concerning their roles and applications. CYPs are now recognized as a central theme of evolutionary strategies for producing attractant and deterrent chemicals, in producing natural products and their detoxification. As noted above, some of the earliest mutations introduced in Penicillium to improve the titre involved altering the flux via mutations in CYP [1] and fungal stereo- and regio-specific steroid CYP biotransformations were important allowing industrial production of corticosteroids [2] more than 50 years ago. The involvement of CYPs in sterol biosynthesis and steroid biosynthesis has been a focus up to now of drug development via CYP inhibitors. This is especially true of CYP51 (sterol 14α-demethylase), a cytochrome P450 found with an ancestral role in the superfamily and identified in some bacteria, lower eukaryotes, plants and animals [3]. Work at the meeting discussed a second CYP activity across the Kingdoms of Life, the sterol Δ22-desaturases identified as CYP61 in Saccharomyces cerevisiae [4] and now as CYP710 in plants [5].

Rules of CYP family classification were discussed at the conference and are based currently on amino acid sequence identity (>40% for assignment to the same family; http://drnelson.utmem.edu/CytochromeP450.html), except for CYP51 where these rules are relaxed to encompass the CYPs undertaking identical function. A similar rational for sterol Δ22-desaturases could be proposed and functional classification was discussed for other CYPs. However, the ability of one or a few amino acid changes to alter the activity of a CYP where everything else remains the same can make CYP classification more difficult. Where a common biological function, rather than activity, is demonstrated, some reassignment of CYPs to families may become possible, but at which point in the avalanche of emerging sequence information this should be attempted is open to debate.

The following transactions represent many of the presentations at the 8th International Symposium on Cytochrome P450 Biodiversity and Biotechnology concerning CYPs: the interaction between plants and insects, insecticide resistance, resistance to azole fungicides that have regained importance in pathogen control in agriculture, CYP51 as a drug target in trypanosome control, and, for Mycobacterium tuberculosis, CYPs as biomarkers of pollution and in bioremediation, new pathways and roles for CYPs, as well as much new information on structure, function and activity of biodiverse CYPs and their redox partners. These included novel CYP forms, fusion systems and the role of mutant NADPH cytochrome P450 reductase in human steroidogenic diseases. The growing number of CYPs for which their structure is resolved with or without substrates was a subject of important comparative discussion, both for CYP structures involved in streptomycete natural product synthesis and other microbes and for human xenobiotic metabolism CYPs. Genomic analysis is a central tool of modern research and transcriptome studies were presented for many of the plant and insect studies. Developments allowing proteomic evaluation including quantification were presented, a newer tool for the eukaryotic membrane-bound CYP proteins that will be developed to encompass biodiverse systems. Similarly, new bioinformatic approaches were described that should help work through the genomes in a way that more rapidly assists in identifying function.

The symposium continued a tradition of informal scientific discussions and lectures that has seen this scientific community meet in Germany, Japan, U.S.A., France, Denmark, Japan and Wales, and future meetings will continue to be held in a similar spirit and scale. The symposium is especially pleased for those who have discovered a role for CYP in their area of biological study to participate and present their results. One of the last speakers, Philip Daborn from Melbourne, pointed out that, from the meeting, perhaps the P in P450 should indicate passion rather than pigment. The next meeting is to be held in June 2008 in the South of France and anyone interested in participating should contact Professor René Feyereisen (rfeyer@sophia.inra.fr).

8th International Symposium on Cytochrome P450 Biodiversity and Biotechnology: Independent Meeting held at Swansea Medical School, Swansea, Wales, U.K., 23–27 July 2006. Organized and Edited by D. Kelly, D. Lamb and S. Kelly (Swansea, U.K.).

Abbreviations

     
  • CYP

    cytochrome P450

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