Synthesis of 19-Hydroxyarachidonic Acid by Fungal Peroxygenases: An Experimental and Computational Study.

ABSTRACT: Hydroxylated derivatives of arachidonic acid play crucial roles in physiology and inflammation response, with distinct biological effects for (R)- and (S)-enantiomers, highlighting their pharmaceutical relevance. Here, recombinant unspecific peroxygenases (UPOs) are harnessed-from the fungi Coprinopsis cinerea (rCciUPO) and Agrocybe aegerita (rAaeUPO), and the rAaeUPO engineered variants A77L, A77T, and A77N-to regio- and enantio-selectively hydroxylate arachidonic acid. rCciUPO and rAaeUPO primarily produced ω-1 and ω-2 hydroxy derivatives, with certain overoxidation to keto forms, while the rAaeUPO variants show enhanced regioselectivity to ω-1 hydroxylation and minor overoxidation. Remarkably, A77L exhibited very good enantioselectivity, yielding 92% of the (S)-enantiomer of 19-hydroxya

SUBMITTER: Gonzalez-Benjumea A 

PROVIDER: S-EPMC12302323 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature