Microbial anaerobic
oxidation of alkanes intrigues the scientific
community by way of its impact on the global carbon cycle, and its
biotechnological applications. Archaea are proposed to degrade short-
and long-chain alkanes to CO
2
by reversing methanogenesis,
a theoretically reversible process. The pathway would start with alkane
activation, an endergonic step catalyzed by methyl-coenzyme M reductase
(MCR) homologues that would generate alkyl-thiols carried by coenzyme
M. While the methane-generating MCR found in methanogens has been
well characterized, the enzymatic activity of the putative alkane-fixing
counterparts has not been validated so far. Such an absence of biochemical
investigations contrasts with the current explosion of metagenomics
data, which draws new potential alkane-oxidizing pathways in various
archaeal phyla. Therefore, validating the physiological function of
these putative alkane-fixing machines and investigating how their
structures, catalytic mechanisms, and cofactors vary depending on
the targeted alkane have become urgent needs. The first structural
insights into the methane- and ethane-capturing MCRs highlighted unsuspected
differences and proposed some explanations for their substrate specificity.
This Perspective reviews the current physiological, biochemical, and
structural knowledge of alkyl-CoM reductases and offers fresh ideas
about the expected mechanistic and chemical differences among members
of this broad family. We conclude with the challenges of the investigation
of these particular enzymes, which might one day generate biofuels
for our modern society.