7nf4
Structure of A. niger Fdc T395M R435P P438W variant (AnFdcII) in complex with prFMN
Structural highlights
FunctionFDC1_ASPNC Catalyzes the reversible decarboxylation of aromatic carboxylic acids like ferulic acid, p-coumaric acid or cinnamic acid, producing the corresponding vinyl derivatives 4-vinylphenol, 4-vinylguaiacol, and styrene, respectively, which play the role of aroma metabolites.[HAMAP-Rule:MF_03196][1] Publication Abstract from PubMedIsobutene is a high value gaseous alkene used as fuel additive and a chemical building block. As an alternative to fossil fuel derived isobutene, we here develop a modified mevalonate pathway for the production of isobutene from glucose in vivo. The final step in the pathway consists of the decarboxylation of 3-methylcrotonic acid, catalysed by an evolved ferulic acid decarboxylase (Fdc) enzyme. Fdc belongs to the prFMN-dependent UbiD enzyme family that catalyses reversible decarboxylation of (hetero)aromatic acids or acrylic acids with extended conjugation. Following a screen of an Fdc library for inherent 3-methylcrotonic acid decarboxylase activity, directed evolution yields variants with up to an 80-fold increase in activity. Crystal structures of the evolved variants reveal that changes in the substrate binding pocket are responsible for increased selectivity. Solution and computational studies suggest that isobutene cycloelimination is rate limiting and strictly dependent on presence of the 3-methyl group. Directed evolution of prenylated FMN-dependent Fdc supports efficient in vivo isobutene production.,Saaret A, Villiers B, Stricher F, Anissimova M, Cadillon M, Spiess R, Hay S, Leys D Nat Commun. 2021 Sep 6;12(1):5300. doi: 10.1038/s41467-021-25598-0. PMID:34489427[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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