α-Oxidative decarboxylation of fatty acids catalysed by cytochrome P450 peroxygenases yielding shorter-alkyl-chain fatty acids

Abstract

Shorter-alkyl-chain fatty acids such as tridecanoic acid or lauric acid were produced from myristic acid by CYP152 peroxygenases.

Preparative Asymmetric Synthesis of Canonical and Non‐canonical α‐amino Acids Through Formal Enantioselective Biocatalytic Amination of Carboxylic Acids

“…[6,19b-d,20] Two regioselective a-hydroxylases (CYP SPa and P450 CLA ), [19b,c] both from the cytochrome P450 family 152 (CYP152), [6] were selected and tested for hydroxylation of 1 a-11 a. Noteworthy, both enzymes can utilize H 2 O 2 as oxidant, [6,19b,c,20] which improves atom economy (no recycling of NAD(P)H or sacrificial co-substrates needed), simplicity as well as scalability of the reaction (no additional energy input required for gas to liquid transfer of O 2 ). [6,19b-d,20] Two regioselective a-hydroxylases (CYP SPa and P450 CLA ), [19b,c] both from the cytochrome P450 family 152 (CYP152), [6] were selected and tested for hydroxylation of 1 a-11 a. Noteworthy, both enzymes can utilize H 2 O 2 as oxidant, [6,19b,c,20] which improves atom economy (no recycling of NAD(P)H or sacrificial co-substrates needed), simplicity as well as scalability of the reaction (no additional energy input required for gas to liquid transfer of O 2 ).…”

“…Selected biocatalytic cascades for the asymmetric synthesis of enantiopure a-AAs involving an initial oxyfunctionalization step. [6] In case of 11 a, 54% of substrate was recovered after the of isolated and dried products (a-HA, ß-OH and others) and the maximum theoretical yields [mg] obtained after full conversion of 1 a-10 a into the respective a-HAs (1 b-10 b). utilization in detail, time studies were performed for the conversion of 1 a, 3 a and 5 a on 50 mL scale (see Figures 1, S13 and S42).…”

“…Heme-peroxygenase catalyzed formation of C-1 FAs proceeds via a-hydride abstraction from the respective a-HA intermediate [28] yielding an a-keto acid product, which can further undergo decarboxylation at elevated concentrations of H 2 O 2 (Scheme 3). [6,28] To prove the origin of C1-FAs/C1-a-HAs, prompted us to investigate conversion of isolated 7 b/ 8 b (from module 1), which resulted in formation of 16 to 22% of over-oxidized/decarboxylated products [6,28] To prove the origin of C1-FAs/C1-a-HAs, prompted us to investigate conversion of isolated 7 b/ 8 b (from module 1), which resulted in formation of 16 to 22% of over-oxidized/decarboxylated products …”

“…[1d,2] The substitution of fossil feedstocks can have a significant impact on achieving a safer and more sustainable production. [5] The a-carbon has rarely been targeted for chemical/biological hydroxylation, [6] although selective a-functionalization affords versatile a-hydroxy acids (a-HAs; 1 b-13 b; Scheme 1), e. g., for the production of biodegradable polyesters (PLA derivatives), pharmaceuticals, antimicrobial agents and natural products. Oxy-functionalizations of FAs focused so far mainly on the w-carbon to produce polyester synthons (fatty alcohols and diacids).…”

“…50% yield; Scheme 1 B). [6,8,19] Herein, we show the development of a three-step linear biocascade for the atom-efficient formal asymmetric a-amination of saturated FAs into enantiopure l-a-AAs in one-pot, on preparative scale, using mild reaction conditions, renewable feedstocks, reagents and catalysts (Scheme 2). [17] Still, many of these routes are based on petroleum-derived feedstocks such as benzenes, olefins, aldehydes or a-HAs (Scheme 2).…”