Styrene Oxide Isomerase‐Catalyzed Meinwald Rearrangement in Cascade Biotransformations: Synthesis of Chiral and/or Natural Chemicals

Abstract

Styrene oxide isomerase (SOI) catalyzes the Meinwald rearrangement of aryl epoxides to carbonyl compounds via a 1,2-trans-shift in a stereospecific manner. A number of cascade biotransformations with SOI-catalyzed epoxide isomerization as a key step have been developed to convert readily available substrates into valuable chiral chemicals. Cascade conversion of terminal or internal alkenes into chiral acids, alcohols or amines was achieved, which involved SOIcatalyzed enantio-retentive isomerization of terminal epoxides via 1,2-H shift, or internal epoxides via 1,2-methyl shift. SOI-involved cascades were also developed to convert racemic epoxides into chiral acids or amines via dynamic kinetic resolution. Additionally, combining SOI-catalyzed isomerization with enantioselective CÀ C bond forming enzymes enabled the synthesis of chiral amino acids or amino alcohols from racemic epoxides. Finally, integration of SOI-involved cascades with biosynthesis pathways allowed for the direct utilization of renewable substrates for the sustainable synthesis of high-value natural chemicals such as alcohols, acids, and esters.

Cryptic Cerulenin Rearrangement in Ketosynthase Covalent Inhibition

“…8 This alphadiketone could be formed by a Meinwald rearrangement of the epoxide catalyzed by a Lewis acid or catalyzed by enzymes. 25,26 A B. subtilis FabF crystal soaked with cerulenin with a resolution of 1.67 Å (PDB ID: 4LS7) delineated the proximity (a distance of 2.8 Å) of a water molecule (part of the water network within a vacant pocket) to the unreacted epoxide, which could potentiate the water molecule to facilitate acidcatalyzed Meinwald rearrangement (Figure S14). Additionally, our lab recently obtained a crystal structure (PDB ID: 8SMS) of the cross-linked complex between E. coli FabB and AcpP tethering a cerulenin cross-linker, which unambiguously depicted the attack at C3 by FabB Cys163 to open the epoxide.…”

“…subtilis FabF identified a unique linkage (C3 in Figure S3b) hemithioacetal, which could be the product of Cys163 attacking an alpha-diketone . This alpha-diketone could be formed by a Meinwald rearrangement of the epoxide catalyzed by a Lewis acid or catalyzed by enzymes. , A B. subtilis FabF crystal soaked with cerulenin with a resolution of 1.67 Å (PDB ID: 4LS7) delineated the proximity (a distance of 2.8 Å) of a water molecule (part of the water network within a vacant pocket) to the unreacted epoxide, which could potentiate the water molecule to facilitate acid-catalyzed Meinwald rearrangement (Figure S14).…”

Enantiodivergent Functionalization of Aryl Alkenes into Diverse Biarylalkanoic Acids by Integrating Biocatalytic Cascades with Chemocatalysis

“…We commenced our study by establishing the enantiodivergent biocatalytic functionalization of 3-bromo-α-methylstyrene 1 to produce ( S )- or ( R )-2-(3-bromophenyl)­propanoic acid 4 . The involved biocascades consist of (i) an enantioselective epoxidation of 1 to 2 catalyzed by styrene monooxygenase (SMO), (ii) an enantio-retentive Meinwald rearrangement of 2 catalyzed by styrene oxide isomerase (SOI) to generate chiral aldehyde 3 , , and (iii) nonenantioselective oxidation of 3 by aldehyde dehydrogenase (ALDH) to afford the desired acid 4 (Figure a).…”

Structural basis of the Meinwald rearrangement catalysed by styrene oxide isomerase

“…These features together make SOI an ideal biocatalyst. The value of SOI for the production of carbonyl compounds from aryl epoxides by means of the Meinwald rearrangement reaction has been demonstrated 8 . In an example, SOI was used for the biocatalytic synthesis of aldehydes via single-step reactions using cell-free extracts or whole cells.…”

“…First, there are very few unique enzymes that can catalyse the isomerization of an epoxide to an aldehyde. Apart from SOI 8,9 and quinolone epoxide rearrangement protein (PenF) 10 from the penigequinolone synthesis pathway, no other enzymes have been reported to catalyse Meinwald rearrangements. Second, SOI has a broad substrate range and may therefore be used for the production of a variety of organic molecules, including new compounds (Extended Data Fig.…”