Embedded Files
Styrene Oxide Isomerase as a Biocatalyst for Meinwald rearrangement
Styrene oxide isomerase (SOI) catalyze the Meinwald rearrangement—a reaction widely used in industry and also potential solution for styrene-based plastics waste management. This chemical reaction usually requires the use of harsh conditions and suffers from low yields due to side reactions and poor regio-selectivity and stereo-specificity. SOI catalyse the same reaction under mild biological conditions and with higher specificity, and thereby making it as high-value biocatalyst for sustainable, eco-friendly chemical processes in industrial applications. We determined high-resolution cryo-EM structures of SOI, and illustrate its trimeric assembly mediated ferric haem b present at the interface of each subunit (Khanppnavar, Choo, Hagedoorn et al., 2024). Hydrophobic catalytic pocket, along with key residues, provides substrate specificity, and Fe(III) acts as the lewis acid by binding to the epoxide oxygen. This structural information, combined with other biophysical studies, provide mechanistic insights on Meinwald rearrangement catalysed by SOI.
Depiction of the cryo-EM structure of styrene oxide isomerase (SOI, PDB ID: 8PNV) and its role in the industrially important 'Meinwald rearrangement' reaction. SOI catalyzes the synthesis of high-value 'aryl acetaldehydes' from inexpensive 'aryl epoxides.'
Dynamic Evolution in Vitamin B5 Biosynthesis Pathways
Microbial Vitamin B5 biosynthesis pathways which are also involved in regulation virulence behavior, considered as a promising candidate for the development of safe and broad specific antimicrobial agent. We show P. aeruginosa, and other bacterial species seems to acquire or lose gene copies for this important metabolic pathway. Higher gene duplications or gene lose frequency was seen for ketopantoate reductase (KPR), an enzyme that catalyases NADPH-dependent rate-limiting reaction (Khanppnavar et al., 2020). We further show that NADPH-cofactor mediated conformational changes seen in KPR is vital for substrate binding, and this ordered-substrate binding cooperativity mechanism is evolved to attain redox cofactor selectivity (Khanppnavar et al., 2020, Choudhury, Khanppnavar et al., 2022).
An overview of microbial Vitamin B5 biosynthesis pathways, highlighting the key enzymes responsible for synthesizing this essential vitamin from pyruvate and L-aspartate. Notably, many microbial species possess multiple copies of ketopantoate reductase compared to other enzymes, suggesting that dynamic redox balance (NADPH/NADH) played a role in the evolutionary adaptation of this pathway.
Steady-state kinetic analysis of ketopantoate reductase (KPR) reveals cooperative-ordered substrate binding mechanisms. NADPH-mediated conformational changes regulate the binding affinity of substrate ketopantoate (KPL), a feature that has evolved to ensure redox cofactor specificity.
References:
1. Khanppnavar B.*, Choo J. P. S.*, Hagedoorn P. L.*, Smolentsev G., Kumaran S., Tischler D., Winkler F., Korkhov V. M., Li Z., Kammerer R., Li X. Structural basis of the Meinwald rearrangement catalyzed by styrene oxide isomerase. Nature Chemistry (2024). https://doi.org/10.1038/s41557-024-01523-y *Co-first authors
2. Choudhury A*., Khanppnavar B.*, Datta S. Crystallographic and biophysical analyses of Pseudomonas aeruginosa ketopantoate reductase: Implications of ligand-induced conformational changes in cofactor recognition. Biochimie (2022). https://doi.org/10.1016/j.biochi.2021.10.015 *Co-first authors
3. Khanppnavar B., Chatterjee R., Choudhary G. B., Datta S. Genome-wide survey and crystallographic analysis suggests a role for both horizontal gene transfer and duplication in pantothenate biosynthesis pathways. BBA-General Subjects (2019) https://doi.org/10.1016/j.bbagen.2019.05.017
Page updated
Google Sites
Report abuse