Structural insights into the role of the acid-alcohol pair of residues required for dioxygen activation in cytochrome P450 enzymes

Structure of the fungal hydroxylase, CYP505A30, and rational transfer of mutation data from CYP102A1 to alter regioselectivity

“…Similar to the crystal structure of CYP102A1 in complex with palmitoleic acid 4 , a distance of approximately 8 Å between the haem and the substrate indicates that this does not, however, constitute a productive binding orientation. With the exception of the catalytic acidalcohol pair (T274, E273) 24 (Figure S18), the substrate channel is lined mainly by non-polar, aliphatic amino acids such as valine, (iso)leucine and phenylalanine (Figure S20). Despite the low overall sequence identity between CYP505A30 and CYP102A1, the active site channel leading to the haem domain is highly conserved, with only 3 amino acid differences, where alanine residues of CYP102A1 are substituted by bigger amino acids I334, I336 and V88 in CYP505A30 (Figure 2).…”

Epoxidation and late-stage C-H functionalization by P450 TamI is mediated by variant heme-iron oxidizing species

“…However, Thr253 resides at the adjacent position that could contribute to the I-helix proton relay network or supplant Thr252 if absent. 13 Mutation of the conserved alcohol residue in P450s is thought to interrupt the second proton transfer, resulting in accumulation of the Cpd 0 species, and diminishing substrate oxidation rates while increasing uncoupling of the enzyme and hydrogen peroxide formation. 9,11,13 For example, P450cam catalyzes hydroxylation of its native substrate camphor with high levels of efficiency.…”

“…13 Mutation of the conserved alcohol residue in P450s is thought to interrupt the second proton transfer, resulting in accumulation of the Cpd 0 species, and diminishing substrate oxidation rates while increasing uncoupling of the enzyme and hydrogen peroxide formation. 9,11,13 For example, P450cam catalyzes hydroxylation of its native substrate camphor with high levels of efficiency. However, its variant T252A produces little to no hydroxylated product and instead, was found capable of performing olefin epoxidation.…”

Rhodamine B oxidation promoted by P450-bioinspired Jacobsen catalysts/cellulose systems

“…By the mid-20th century, it was found that many biological processes from cellular respiration to photosynthesis are centered around redox reactions. [1][2][3] In this context, P450 cytochromes (CYP) are a class of monooxygenase enzymes, characterized by the presence of iron(III) protoporphyrin IX, the enzyme's active site, which metabolizes several classes of organic compounds (e.g. pollutants and drugs) in biological systems.…”

“…pollutants and drugs) in biological systems. [1][2][3][4][5][6][7][8][9] In the attempt to mimic the CYP reactions, many researchers use synthetic models called 'bioinspired catalysts' to reproduce reactions catalysed by these enzymes. While in nature, metalloenzyme-catalysed oxidations oen exhibit exquisite substrate specicity, as well as regioselectivity and/or stereoselectivity, synthetic bioinspired or biomimetic systems may have broader substrate scope and tunable selectivity, which make them challenging protagonists of near-future environmentally friendly catalytic chemistry.…”