Structure of RhlG, an Essential β-Ketoacyl Reductase in the Rhamnolipid Biosynthetic Pathway of Pseudomonas aeruginosa

摘要: Abstract Rhamnolipids are extracellular biosurfactants and virulence factors secreted by the opportunistic human pathogen Pseudomonas aeruginosa that required for swarming motility. The rhlG gene is essential rhamnolipid formation, RhlG enzyme thought to divert fatty acid synthesis intermediates into biosynthetic pathway based on its similarity FabG, β-ketoacyl-acyl carrier protein (ACP) reductase of type II synthesis. Crystallographic analysis reveals overall structures RhlG·NADP+ FabG·NADP+ complexes indeed similar, but there key differences related function. does not undergo conformational changes upon NADP(H) binding at active site in FabG structural basis negative allostery. Also, acyl chain-binding pocket narrow rigid compared with larger, flexible substrate-binding subdomain FabG. Finally, lacks a positively charged/hydrophobic surface feature adjacent found enzymes like recognize ACP catalyzed NADPH-dependent reduction β-ketodecanoyl-ACP β-d-hydroxydecanoyl-ACP. However, was 2000-fold less than carrying out same reaction. These biochemical studies establish as β-ketoacyl SDR superfamily further suggest carry substrates RhlG.