Relative to the atmosphere, much of the aerobic ocean is supersaturated with methane; however, the source of this important greenhouse gas remains enigmatic. Catabolism of methylphosphonic acid by phosphorus-starved marine microbes, with concomitant release of methane, has been suggested to explain this phenomenon, yet methylphosphonate is not a known natural product, nor has it been detected in natural systems. Further, its synthesis from known natural products would require unknown biochemistry. Here we show that the marine archaeon Nitrosopumilus maritimus encodes a pathway for methylphosphonate biosynthesis and that it produces cell-associated methylphosphonate esters. The abundance of a key gene in this pathway in metagenomic datasets suggests that methylphosphonate biosynthesis is relatively common in marine microbes, providing a plausible explanation for the methane paradox.
Beta-amino acids are widely used building blocks in both natural and synthetic compounds. Aromatic beta-amino acids can be biosynthesized directly from proteinogenic alpha-amino acids by the action of MIO (4-methylideneimidazole-5-one)-based aminomutase enzymes. The uncommon cofactor MIO plays a role in both ammonia lyases and 2,3-aminomutases; however, the precise mechanism of the cofactor has not been resolved. Here we provide evidence that the electrophilic cofactor uses covalent catalysis through the substrate amine to direct the elimination and subsequent readdition of ammonia. A mechanism-based inhibitor was synthesized and the X-ray cocomplex structure was determined to 2.0 A resolution. The inhibitor halts the chemistry of the reverse reaction, providing a stable complex that establishes the mode of substrate binding and the importance of tyrosine 63 in the chemistry. The proposed mechanism is consistent with the biochemistry of aminomutases and ammonia lyases and provides strong support for an amine-adduct mechanism of catalysis for this enzyme class.
Methylphosphonate synthase is a non-heme iron-dependent
oxygenase
that converts 2-hydroxyethylphosphonate (2-HEP) to methylphosphonate.
On the basis of experiments with two enantiomers of a substrate analog,
2-hydroxypropylphosphonate, catalysis is proposed to commence with
stereospecific abstraction of the pro-S hydrogen
on C2 of the substrate. Experiments with isotopologues of 2-HEP indicate
stereospecific hydrogen transfer of the pro-R hydrogen
at C2 of the substrate to the methyl group of methylphosphonate. Kinetic
studies with these substrate isotopologues reveal that neither hydrogen
transfer is rate limiting under saturating substrate conditions. A
mechanism is proposed that is consistent with the available data.
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