TY - GEN A1 - Aranda, Carmen A1 - Ullrich, René A1 - Kiebist, Jan A1 - Scheibner, Katrin A1 - Río, José C. del A1 - Hofrichter, Martin A1 - Martínez, Angel T. A1 - Gutiérrez, Ana T1 - Selective synthesis of the resveratrol analogue 4,4′-dihydroxy-trans-stilbene and stilbenoids modification by fungal peroxygenases T2 - Catalysis Science & Technology N2 - This work gives first evidence that the unspecific peroxygenases (UPOs) from the basidiomycetes Agrocybe aegerita (AaeUPO), Coprinopsis cinerea (rCciUPO) and Marasmius rotula (MroUPO) are able to catalyze the regioselective hydroxylation of trans-stilbene to 4,4′-dihydroxy-trans-stilbene (DHS), a resveratrol (RSV) analogue whose preventive effects on cancer invasion and metastasis have very recently been shown. Nearly complete transformation of substrate (yielding DHS) was achieved with the three enzymes tested, using H2O2 as the only co-substrate, with AaeUPO showing exceptionally higher total turnover number (200 000) than MroUPO (26 000) and rCciUPO (1400). Kinetic studies demonstrated that AaeUPO was the most efficient enzyme catalyzing stilbene dihydroxylation with catalytic efficiencies (kcat/Km) one and two orders of magnitude higher than those of MroUPO and rCciUPO, so that 4-hydroxystilbene appears to be the best UPO substrate reported to date. In contrast, the peroxygenase from the ascomycete Chaetomium globosum (CglUPO) failed to hydroxylate trans-stilbene at the aromatic ring and instead produced the trans-epoxide in the alkenyl moiety. In addition, stilbenoids such as pinosylvin (Pin) and RSV were tested as substrates for the enzymatic synthesis of RSV from Pin and oxyresveratrol (oxyRSV) from both RSV and Pin. Overall, lower conversion rates and regioselectivities compared with trans-stilbene were accomplished by three of the UPOs, and no conversion was observed with CglUPO. The highest amount of RSV (63% of products) and oxyRSV (78%) were again attained with AaeUPO. True peroxygenase activity was demonstrated by incorporation of 18O from H218O2 into the stilbene hydroxylation products. Differences in the number of phenylalanine residues at the heme access channels seems related to differences in aromatic hydroxylation activity, since they would facilitate substrate positioning by aromatic-aromatic interactions. The only ascomycete UPO tested (that of C. globosum) turned out to have the most differing active site (distal side of heme cavity) and reactivity with stilbenes resulting in ethenyl epoxidation instead of aromatic hydroxylation. The above oxyfunctionalizations by fungal UPOs represent a novel and simple alternative to chemical synthesis for the production of DHS, RSV and oxyRSV. KW - Peroxygenase Y1 - 2018 U6 - https://doi.org/10.1039/C8CY00272J SN - 2044-4761 SN - 2044-4753 VL - 9 IS - 8 SP - 2394 EP - 2401 ER - TY - GEN A1 - Aranda, Carmen A1 - Olmedo, Andrés A1 - Kiebist, Jan A1 - Scheibner, Katrin A1 - Río, José C. del A1 - Martínez, Angel T. A1 - Gutiérrez, Ana T1 - Selective Epoxidation of Fatty Acids and Fatty Acid Methyl Esters by Fungal Peroxygenases T2 - CHEMCATCHEM N2 - Recently discovered fungal unspecific peroxygenases from Marasmius rotula and Chaetomium globosum catalyze the epoxidation of unsaturated fatty acids (FA) and FA methyl esters (FAME), unlike the well‐known peroxygenases from Agrocybe aegerita and Coprinopsis cinerea. Reactions of a series of unsaturated FA and FAME with cis‐configuration revealed high (up to 100 %) substrate conversion and selectivity towards epoxidation, although some significant differences were observed between enzymes and substrates with the best results being obtained with the C. globosum enzyme. This and the M. rotula peroxygenase appear as promising biocatalysts for the environmentally‐friendly production of reactive FA epoxides given their self‐sufficient monooxygenase activity and the high conversion rate and epoxidation selectivity. KW - Peroxygenase Y1 - 2018 U6 - https://doi.org/10.1002/cctc.201800849 SN - 1867-3899 VL - 10 IS - 18 SP - 3964 EP - 3968 ER -