From Alkanes to Carboxylic Acids: Terminal Oxygenation by a Fungal Peroxygenase

Abstract

A new heme-thiolate peroxidase catalyzes the hydroxylation of n-alkanes at the terminal position-a challenging reaction in organic chemistry-with H2 O2 as the only cosubstrate. Besides the primary product, 1-dodecanol, the conversion of dodecane yielded dodecanoic, 12-hydroxydodecanoic, and 1,12-dodecanedioic acids, as identified by GC-MS. Dodecanal could be detected only in trace amounts, and 1,12-dodecanediol was not observed, thus suggesting that dodecanoic acid is the branch point between mono- and diterminal hydroxylation. Simultaneously, oxygenation was observed at other hydrocarbon chain positions (preferentially C2 and C11). Similar results were observed in reactions of tetradecane. The pattern of products formed, together with data on the incorporation of (18) O from the cosubstrate H2 (18) O2 , demonstrate that the enzyme acts as a peroxygenase that is able to catalyze a cascade of mono- and diterminal oxidation reactions of long-chain n-alkanes to give carboxylic acids.

Biocatalytic Oxidation Reactions: A Chemist's Perspective

“…Controlling the regioselectivity of amacrolide hydroxylation with ester directing groups. [28] which was soon followed by further peroxygenases from other sources,s uch as Marasmius rotula (MroUPO) [34] or Coprinopsis cinerea (CciUPO). [35] These enzymes exhibit interesting differences in their selectivity:A lkane hydroxylation by AaeUPO occurs preferentially in w-1 and w-2 position whereas MroUPO is highly selective for the terminal w position.…”

Dual‐Functional Small Molecules for Generating an Efficient Cytochrome P450BM3 Peroxygenase

“…The catalytic mechanism of natural peroxidases and peroxygenases has been well described ,. For instance, the peroxygenase from Agrocybe aegerita (AaeUPO) uses its distal Glu196 to promote the deprotonation of the peroxocomplex and the subsequent heterolytic cleavage of the O−O bond, resulting in the active compound I that is responsible for substrate oxidation (Figure A).…”

Fatty Acid Chain Shortening by a Fungal Peroxygenase

“…Since then, similar UPO proteins have been purified from other basidiomycetes and ascomycetes such as Coprinellus radians , Marasmius rotula and Chaetomium globosum ; and almost 3000 related sequences (from sequenced genomes and environmental samples) are currently available in databases . The peroxygenase from M. rotula ( Mro UPO) shows several special features compared to other UPOs, for example, the inability to oxidize halides, less pronounced capacity to oxygenate aromatics, and the unique ability for terminal hydroxylation of n ‐alkanes …”

“…The chain‐shortening reaction described here must be added to the repertoire of reactions that versatile fungal peroxygenases catalyze on linear and cyclic aliphatic compounds, in addition to aromatic compounds . The availability of a heterologous expression system for Mro UPO will permit to improve the catalytic properties of this promising enzyme, for example, in chain‐shortening and/or alkane terminal hydroxylation reactions, using the protein engineering tools recently applied to Aae UPO …”