Regioselective Biocatalytic Hydroxylation of Fatty Acids by Cytochrome P450s

Abstract

Cytochrome P450 enzymes catalyze a broad set of C-H activation reactions, the most prominent being hydroxylation. This review provides an overview of the regioselectivity (CH 3 -terminal, in-chain, and carboxylate-terminal) and the optical purity of the hydroxylation products obtained from fatty acids as far as described, focusing on systems close to preparative application. Graphical Abstract

Controlling the Regioselectivity of Fatty Acid Hydroxylation (C10) at α‐ and β‐Position by CYP152A1 (P450Bsβ) Variants

“…Importantly, the site of reaction may be altered by mutagenesis . Regioselective non‐terminal hydroxylations of fatty acids however remain challenging as the only selective systems known attack the chemically distinct α‐ or ω‐positions …”

“…[11,12] Regioselective non-terminal hydroxylations of fatty acids however remain challenging as the only selective systems known attack the chemically distinct αor ωpositions. [13] CYPs rely on molecular oxygen (O 2 ) as well as the transfer of two electrons from NADPH, to produce the reactive heme intermediate (compound I). [14] This electron transfer is enabled by either distinct electron transfer proteins or by a specific domain attached to the heme domain like in case of selfsufficient P450s such as BM3.…”

“…[16][17][18][19][20][21] In this case, no electron transfer system is required and uncoupling reactions are avoided to a large extend. [13] In our search for cytochrome P450s for regioselective inchain hydroxylation of fatty acids we turned our attention to the CYP152 family. These enzymes catalyze fatty acid hydroxylation mainly but not exclusively at the α-position to the carboxyl terminus.…”

Regio‐ and Enantio‐selective Chemo‐enzymatic C−H‐Lactonization of Decanoic Acid to (S)‐δ‐Decalactone

“…[5,6] Hence,t here is an eed for selective synthetic methods towards HFAs,ideally by direct oxidation of readily available fatty acids.T he chemical oxyfunctionalization of non-activated C À Hb onds in fatty acids is one of the most demanding chemical reactions because of the additional need for regio-selective targeting of one of many methylene groups and demands on enantioselectivity on highly flexible substrates. [8][9][10][11][12] Fore xample,P 450-BM3 has been reported to hydroxylate unsaturated fatty acids (C10:0-C18:0) at positions w-1, w-2, and w-3. [8][9][10][11][12] Fore xample,P 450-BM3 has been reported to hydroxylate unsaturated fatty acids (C10:0-C18:0) at positions w-1, w-2, and w-3.…”

“…[7] In this regard, biocatalysis using P450 monooxygenases (P450s,C YPs) represents an attractive option for selective C À Hb ond activation with the added advantage of mild reaction conditions.C onsequently,f atty acid hydroxylation catalyzed by P450s has been widely investigated, but often suffers from poor regioselectivity and limitation to terminal positions. [8][9][10][11][12] Fore xample,P 450-BM3 has been reported to hydroxylate unsaturated fatty acids (C10:0-C18:0) at positions w-1, w-2, and w-3. [13,14] Some elegant studies using genome mining and protein engineering have sought to address this issue and resulted in new product profiles.…”