New Trends in Fungal Biooxidation

Can peroxygenase and microperoxidase substitute cytochrome P450 in biosensors

“…In contrast to the large number of publications on the bioelectrochemistry of P450 and related sensors, we recently published the first two papers on peroxygenase-based sensors. This new heme-thiolate peroxidase was discovered in the wood-rotting fungus A. aegerita (black poplar mushroom) some years ago and turned out to be a true peroxygenase, efficiently transferring peroxide oxygen to various organic substrates [36][37][38][39][40]. Due to its remarkable ability to peroxygenate aromatic substrates (proven by 18 O-labelling studies with H 2 18 O 2 as the co-substrate) and the very broad substrate spectrum, the enzyme is nowadays mostly referred to as aromatic peroxygenase (APO) 1 or unspecific peroxygenase [41][42][43][44].…”

“…AaeAPO can be regarded as a functional hybride of both enzyme types [40,44,45,54,55]. The cycle may rapidly lead via Compound 0 to the formation of Compound I.…”

“…AaeAPO has a great biotechnological potential since selective oxo-functionalizations are among the most challenging and desired reactions in organic synthesis [40]. Depending on the particular substrate and the reaction conditions, it catalyses not only diverse peroxygenations but also one-electron abstractions and halogenations (Fig.…”

One-pot synthesis of human metabolites of SAR548304 by fungal peroxygenases

“…30,35,50,66 The formation of the postulated N-formyl might be the result of a second hydroxylation of the same Nmethyl group (prior to the hemiaminal decay) and subsequent water release from the resulting unstable geminal alcohol as it is known for the oxidation of alcohols by UPOs (Scheme 2). 51 Finally, SAR548304 (1) was converted into 70% 2, 13% 14 and 15% 15. By a subsequent acidic hydrolysis of 14 and 15, the yield of 2 could be increased up to 85%, which fully agrees with the results of the reaction optimization on analytical scale.…”

“…43,44 It was shown that the reactions catalyzed by UPOs are similar to P450 transformations [45][46][47][48][49] and several studies have suggested a broad scope of UPOs as synthesis tools for metabolite preparation 50 and other synthetic applications. 51 Thus, a number of marketed drugs, for example, propranolol, naproxen or sildenafil were directly converted to their corresponding human drug metabolites. A first example for the application of UPO on preparative scale is the efficient one-step preparation of 4 0 -OH-diclofenac-d 6 , required as internal standard for LC-MS-based P450 inhibition screenings.…”