Cyanobacterial alkane biosynthesis further expands the catalytic repertoire of the ferritin-like 'di-iron-carboxylate' proteins

Enzymes that activate dioxygen at carboxylate-bridged non-heme diiron clusters residing within ferritin-like, four-helix-bundle protein architectures have crucial roles in, among other processes, the global carbon cycle (e.g. soluble methane monooxygenase), fatty acid biosynthesis [plant fatty acyl-acyl carrier protein (ACP) desaturases], DNA biosynthesis [the R2 or beta 2 subunits of class la ribonucleotide reductases (RNRs)], and cellular iron trafficking (ferritins). Classic studies on class la RNRs showed long ago how this obligatorily oxidative di-iron/O-2 chemistry can be used to activate an enzyme for even a reduction reaction, and more recent investigations of class lb and lc RNRs, coupled with earlier studies on dimanganese catalases, have shown that members of this protein family can also incorporate either one or two Mn ions and use them in place of iron for redox catalysis. These two strategies - oxidative activation for non-oxidative reactions and use of alternative metal ions-expand the catalytic repertoire of the family, probably to include activities that remain to be discovered. Indeed, a recent study has suggested that fatty aldehyde decarbonylases (ADs) from cyanobacteria, purported to catalyze a redox-neutral cleavage of a C-n aldehyde to the Cn-1 alkane (or alkene) and CO, also belong to this enzyme family and are most similar in structure to two other members with heterodinuclear (Mn-Fe) cofactors. Here, we first briefly review both the chemical principles underlying the O-2-dependent oxidative chemistry of the 'classical' di-iron-carboxylate proteins and the two aforementioned strategies that have expanded their functional range, and then consider what metal ion(s) and what chemical mechanism(s) might be employed by the newly discovered cyanobacterial ADs.