Tunnel engineering of gas-converting enzymes for inhibitor retardation and substrate acceleration

• Published in: Bioresource technology Vol. 394; p. 130248
• Main Authors: Kim, Suk Min, Kang, Sung Heuck, Jeon, Byoung Wook, Kim, Yong Hwan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2024
• ISSN: 0960-8524; 1873-2976
• DOI: 10.1016/j.biortech.2023.130248

[Display omitted] •The review highlights inhibitor tunnels in enzymes, showing industrial promise.•87 % of enzymes have tunnels >5 Å, and their traversal is key for inhibitor access.•Protein structure and tunnel prediction tools are key for substrate tunnel studies.•Tracing inhibitor paths in tunnels rationally aids in upgrading enzyme reactions.•Tunnel engineering boosts enzyme performance by enabling precise enzyme designs. Carbon monoxide dehydrogenase (CODH), formate dehydrogenase (FDH), hydrogenase (H2ase), and nitrogenase (N2ase) are crucial enzymatic catalysts that facilitate the conversion of industrially significant gases such as CO, CO2, H2, and N2. The tunnels in the gas-converting enzymes serve as conduits for these low molecular weight gases to access deeply buried catalytic sites. The identification of the substrate tunnels is imperative for comprehending the substrate selectivity mechanism underlying these gas-converting enzymes. This knowledge also holds substantial value for industrial applications, particularly in addressing the challenges associated with separation and utilization of byproduct gases. In this comprehensive review, we delve into the emerging field of tunnel engineering, presenting a range of approaches and analyses. Additionally, we propose methodologies for the systematic design of enzymes, with the ultimate goal of advancing protein engineering strategies.