Reduction of Chemically Stable Multibonds: Nitrogenase-Like Biosynthesis of Tetrapyrroles.

Abstract

The sophisticated biochemistry of nitrogenase plays a fundamental role for the biosynthesis of tetrapyrrole molecules, acting as key components of photosynthesis and methanogenesis. Three nitrogenase-like metalloenzymes have been characterized to date. Synthesis of chlorophylls and bacteriochlorophylls involves the reduction of the C17-C18 double bond of the conjugated ring system of protochlorophyllide which is catalyzed by the multi-subunit enzyme dark operative protochlorophyllide oxidoreductase (DPOR). Subsequently, biosynthesis of all bacteriochlorophylls requires the reduction of the C7-C8 double bond by a second nitrogenase-like enzyme termed chlorophyllide oxidoreductase (COR). Mechanistically, DPOR and COR make use of a reductase component which links ATP hydrolysis to conformational changes. This dynamic switch protein is triggering the transient association between the reductase and the core catalytic protein complex, thereby facilitating the transduction of electrons via two [4Fe4S] clusters. X-ray crystallographic structural investigations in combination with biochemical experiments revealed the molecular basis of the underlying energy transduction mechanism. The unique nickel-containing tetrapyrrole cofactor F430 is located in the active site of methyl-coenzyme M reductase, which is catalyzing the final step of methane formation in methanogenic archaea. The nitrogenase-like protein NflH/NflD has been proposed to catalyze one or more ring reduction steps during the biosynthesis of F430. The present working hypothesis mirrors a DPOR and COR related enzyme mechanism of NflH/NflD. Furthermore, nfl-encoded proteins were suggested as "simplified" ancestors lying basal in the phylogenetic tree between nitrogenase and DPOR/COR.