Bioengineering of plant (tri)terpenoids: from metabolic engineering of plants to synthetic biology in vivo and in vitro.
Cytochrome P450 monooxygenases (CYPs) form a vast and diverse enzyme class of particular interest in drug development and a high biotechnological potential. Although very diverse in sequence, they share a common structural fold. For the comprehensive and systematic comparison of protein sequences and structures the Cytochrome P450 Engineering Database (CYPED) was established. It was built up based on an extensible data model that enables its functions readily enhanced. The new version of the CYPED contains information on sequences and structures of 8613 and 47 proteins, respectively, which strictly follow Nelson's classification rules for homologous families and superfamilies. To gain biochemical information on substrates and inhibitors, the CYPED was linked to the Cytochrome P450 Knowledgebase (CPK). To overcome differences in the data model and inconsistencies in the content of CYPED and CPK, a metric was established based on sequence similarity to link protein sequences as primary keys. In addition, the annotation of structurally and functionally relevant residues was extended by a reliable prediction of conserved secondary structure elements and by information on the effect of single nucleotide polymorphisms. The online accessible version of the CYPED at http://www.cyped.uni-stuttgart.de provides a valuable tool for the analysis of sequences, structures and their relationships to biochemical properties.