636-36-2Relevant articles and documents
P450Jα: A New, Robust and α-Selective Fatty Acid Hydroxylase Displaying Unexpected 1-Alkene Formation
Armbruster, Julia,Steinmassl, Mathilde,Müller Bogotá, Christina A.,Berg, Gabriele,Nidetzky, Bernd,Dennig, Alexander
, p. 15910 - 15921 (2020/10/29)
Oxyfunctionalization of fatty acids (FAs) is a key step in the design of novel synthetic pathways for biobased/biodegradable polymers, surfactants and fuels. Here, we show the isolation and characterization of a robust FA α-hydroxylase (P450Jα) which catalyses the selective conversion of a broad range of FAs (C6:0-C16:0) and oleic acid (C18:1) with H2O2 as oxidant. Under optimized reaction conditions P450Jα yields α-hydroxy acids all with >95 % regioselectivity, high specific activity (up to 15.2 U mg?1) and efficient coupling of oxidant to product (up to 85 %). Lauric acid (C12:0) turned out to be an excellent substrate with respect to productivity (TON=394 min?1). On preparative scale, conversion of C12:0 reached 83 % (0.9 g L?1) when supplementing H2O2 in fed-batch mode. Under similar conditions P450Jα allowed further the first biocatalytic α-hydroxylation of oleic acid (88 % conversion on 100 mL scale) at high selectivity and in good yields (1.1 g L?1; 79 % isolated yield). Unexpectedly, P450Jα displayed also 1-alkene formation from shorter chain FAs (≤C10:0) showing that oxidative decarboxylation is more widely distributed across this enzyme family than reported previously.
(2R)- and (2S)- 2-hydroxy- hexanoyl and octanoyl-L-homoserine lactones: New highly potent Quorum Sensing modulators with opposite activities
Jeanneau, Erwann,Queneau, Yves,Soulère, Laurent,Zhang, Qiang
supporting information, (2020/10/12)
The synthesis and the QS modulation activity of diastereoisomerically pure 2-hydroxy-N-acyl-L-homoserine lactones (2-OH-AHLs) are unveiled. (2R)- and (2S)- 2-hydroxy-N-hexanoyl-L-homoserine lactone and 2-hydroxy-N-octanoyl-L-homoserine lactone have been identified as very potent QS agonists and antagonists on the Vibrio fischeri-quorum sensing system with opposite activities depending on the configuration of the carbon atom with the hydroxyl group. Flexible molecular docking showed that the (2R)–OH configuration in the antagonist isomer induces new hydrogen bonds with Tyr70 and Asp79, two importantly conserved residues in the LuxR protein family, while the (2S)–OH agonist configuration exhibits a binding mode comparable to the natural ligand 3-oxo-hexanoyl-L-homoserine lactone (OHHL). For the analogs with long alkyl chain 3a and 3b and aromatic analogs, all are antagonists with no effect of the configuration at C-2.
Preparative Asymmetric Synthesis of Canonical and Non-canonical a-amino Acids through Formal Enantioselective Biocatalytic Amination of Carboxylic Acids
Dennig, Alexander,Blaschke, Fabio,Gandomkar, Somayyeh,Tassano, Erika,Nidetzky, Bernd
supporting information, p. 1348 - 1358 (2019/10/28)
Chemical and biocatalytic synthesis of non-canonical a-amino acids (ncAAs) from renewable feedstocks and using mild reaction conditions has not efficiently been solved. Here, we show the development of a three-step, scalable and modular one-pot biocascade for linear conversion of renewable fatty acids (FAs) into enantiopure l-a-amino acids. In module 1, selective a-hydroxylation of FAs is catalyzed by the P450 peroxygenase P450CLA. By using an automated H2O2 supplementation system, efficient conversion (46 to >99%; TTN>3300) of a broad range of FAs (C6:0 to C16:0) into valuable a-hydroxy acids (a-HAs; >90% a-selective) is shown on preparative scale (up to 2.3 gL1 isolated product). In module 2, a redox-neutral hydrogen borrowing cascade (alcohol dehydrogenase/amino acid dehydrogenase) allowed further conversion of a-HAs into l-a-AAs (20 to 99%). Enantiopure l-a-AAs (e.e. >99%) including the pharma synthon l-homo-phenylalanine can be obtained at product titers of up to 2.5 gL1. Based on renewables and excellent atom economy, this biocascade is among the shortest and greenest synthetic routes to structurally diverse and industrially relevant ncAAs.
