In addition Uroz and colleagues reported the presence of oxidoreductase activities in crude cell extracts of Rhodococcus erythropolis W2. They demonstrated that crude cell extracts of R. erythropolis reduced the 3-oxo-substituent of 3-oxo-C14-HSL to yield the corresponding 3-hydroxy derivative, 3-hydroxy-C14-HSL. However, the corresponding R. erythropolis enzyme was not identified. In general the enzyme class of oxidoreductases includes a large family called short-chain dehydrogenases/reductases. For recent reviews see references. Up to date, almost 47,000 examples are known. The SDRs cluster into at least 300 distinct families. SDRs have in general low sequence similarities but they all show a special folding pattern, the Rossmann fold motif for binding to their nucleotide cofactor, NAD or NADP. The 3D-structures display highly similar a/b folding patterns with a central b-sheet. Based on distinct sequence motifs, functional assignments and classifications are possible. The active site is often composed of an Asn-Ser-Tyr- Lys tetrad and the catalytic mechanism usually is a hydrid and proton transfer from or to the nicotinamid and the active site tyrosine residue. The variable C-terminus provides substrate specificity. SDR enzymes play essential roles in a wide range of cellular activities including lipid, amino acid, carbohydrate, cofactor, hormone and xenobiotic metabolisms; but also in redox sensor mechanisms. Today 261 SDR structure entries are available at PDB and of these 159 have been classified as oxidoreductases. Of these 55 are Fulvestrant Estrogen Receptor inhibitor linked to bacteria but only 26 are unique and represent self-contained and genetically unmodified wildtype enzymes; and of these less than 10 appear to utilize NADP as a ligand. Furthermore no metagenome derived SDR structures have been deposited at PDB. Within this work, we attempted to extend our knowledge on SDRs interfering with the bacterial quorum sensing mechanisms using a metagenome-based and structural approach. Therefore we identified a novel oxidoreductase, designated BpiB09, which was able to inactivate the 3-oxo-C12-HSL signaling molecule. The novel metagenome-derived enzyme strongly MK-2206 2HCl Akt inhibitor affected P. aeruginosa biofilm formation and other QS-related phenotypes. BpiB09 enzyme was crystallized and we solved the BpiB09 structure at a resolution of 2.4 A �� together with the cofactor NADP. Structural inspection of BpiB09 reveals that it exhibits a typical SDR fold and the functional signatures of this family of proteins. Further transcriptome analysis of P. aeruginosa cells expressing bpiB09 suggests that it has profound effects on QS related gene expression in this microbe. Our data also showed that as a result of the bpiB09 expression a significant fraction of PAO1 genes were differentially regulated in both strains.