%AMallinson, Sam%AMachovina, Melodie%ASilveira, Rodrigo%AGarcia-BorrĂ s, Marc%AGallup, Nathan%AJohnson, Christopher%AAllen, Mark%ASkaf, Munir%ACrowley, Michael%ANeidle, Ellen%AHouk, Kendall%ABeckham, Gregg%ADuBois, Jennifer%AMcGeehan, John%BJournal Name: Nature Communications; Journal Volume: 9; Journal Issue: 1; Related Information: CHORUS Timestamp: 2022-12-20 10:05:18 %D2018%INature Publishing Group %JJournal Name: Nature Communications; Journal Volume: 9; Journal Issue: 1; Related Information: CHORUS Timestamp: 2022-12-20 10:05:18 %K %MOSTI ID: 10154351 %PMedium: X %TA promiscuous cytochrome P450 aromatic O-demethylase for lignin bioconversion %XAbstract

Microbial aromatic catabolism offers a promising approach to convert lignin, a vast source of renewable carbon, into useful products. Aryl-O-demethylation is an essential biochemical reaction to ultimately catabolize coniferyl and sinapyl lignin-derived aromatic compounds, and is often a key bottleneck for both native and engineered bioconversion pathways. Here, we report the comprehensive characterization of a promiscuous P450 aryl-O-demethylase, consisting of a cytochrome P450 protein from the family CYP255A (GcoA) and a three-domain reductase (GcoB) that together represent a new two-component P450 class. Though originally described as converting guaiacol to catechol, we show that this system efficiently demethylates both guaiacol and an unexpectedly wide variety of lignin-relevant monomers. Structural, biochemical, and computational studies of this novel two-component system elucidate the mechanism of its broad substrate specificity, presenting it as a new tool for a critical step in biological lignin conversion.

%0Journal Article