Engineered myoglobin as a catalyst for atom transfer radical cyclisation

Abstract

Myoglobin was subjected to site-directed mutagenesis and transformed into a catalyst able to perform atom transfer radical reaction. Replacing the iron-coordinating histidine with serine, or introducing small changes inside or...

Radical Cyclization-Initiated Difunctionalization Reactions of Alkenes and Alkynes

“…Pellizzoni and coworkers reported a myoglobin-catalyzed reaction of N-allyl-α-haloamides for the synthesis of γ-lactams in 2022. The reaction of N-allyl-α-haloamides 33 in the presence of Mb H93S (as purified protein and in whole bacterial cells), sodium ascorbate, and sodium phosphate buffer (pH 7.4) produced products 34 in good yields (Scheme 12) [38]. Initial radicals 35 produced by the reaction of N-allyl-2-bromo-propanamide 33 and [Fe II ] of Mb H93S undergo a 5-exo cyclization to give radicals 36 followed by coupling with Br radical from [Fe III ]Br to give products 34.…”

“…Pellizzoni and coworkers reported a myoglobin-catalyzed reaction of N -allyl- α -haloamides for the synthesis of γ -lactams in 2022. The reaction of N -allyl- α -haloamides 33 in the presence of Mb H93S (as purified protein and in whole bacterial cells), sodium ascorbate, and sodium phosphate buffer (pH 7.4) produced products 34 in good yields ( Scheme 12 ) [ 38 ].…”

Synthesizing biomaterials in living organisms

“…Up to now, several metalloenzymes or proteins, such as HRP, 128 hemoglobin (Hb), 129 hemozoin, 130 catalase, 131 and laccases, 132 have been proven to catalyze ATRP. Since enzymes can be feasibly engineered through bioengineering techniques such as artificial mutagenesis 133 and genetic engineering, there is promising potential to revolutionize the enzymatic efficiency of engineered enzymes for radical polymerization.…”

“…For instance, through site-directed mutagenesis, the transformation of myoglobin into a catalyst for intramolecular atom transfer radical additions has been reported. 133 However, an interesting avenue worth further exploration involves genetically engineering cells to overproduce myoglobin and employ it as a catalyst for similar reactions. Fourth, considering the substantial capabilities of artificial intelligence (AI) techniques in expediting the prediction and discovery of biomaterials, 74 utilizing AI models for optimizing the design and discovery process of in vivo synthesized biomaterials appears to be a promising option in the future.…”

Hot off the press

“…Serine mutation of a heme-coordinating residue of myoglobin has produced an artificial metalloenzyme capable of performing atom transfer radical cyclisation reactions. 36 The engineered myoglobin was shown to catalyse the synthesis of γ-lactams by the addition of C–Cl or C–Br bonds (Scheme 7) across an alkene.…”