World’s first discovery of a controlling mechanism for radical enzyme reactions by an activated form of vitamin B12 – anticipated application to the material production of high-quality clothing fiber

May 29(Tue), 2018

Naoki Shibata, an associate professor at the University of Hyogo, and Yoshiki Higuchi, a professor at the University of Hyogo (both visiting research fellows at RIKEN, the Institute of Physical and Chemical Research at the time of this research), along with Tetsuo Toraya, an emeritus professor at Okayama University, made the first discovery of a reaction mechanism in which an activated form of vitamin B12 controls the radical during enzyme reactions. This discovery was reported online in “Angewandte Chemie International Edition” (a peer-reviewed journal by the German Chemical Society) on May 25, 2018.

One of the activated forms of vitamin B12, adenosyl B12, utilizes a highly active species called radicals to catalyze enzyme reactions that are chemically difficult to proceed. While there is an advantage to this strategy where high reactivity can be expected for enzymes by utilizing the radical, there is also a possible side reaction that may easily cause inactivation. In the past, the adenosyl B12-dependent enzymes were considered to have structures that tend to prevent side reactions from happening. However, as an accurate steric structure of the enzyme-adenosyl B12 complex was not available, the details were never understood.
In this research, accurate X-ray structures of adenosyl B12-dependent diol dehydratase and ethanolamine ammonia‐lyase in complexes with adenosyl B12 were analyzed at their atomic levels at SPring-8, a synchrotron radiation facility. The structures revealed for the very first time that the a-side chain, one of the peripheral amide side chains, of the corrin ring interacts with a certain amino-acid residue surrounding it to maintain the stable structure of generated adenosyl radicals to control side reactions from happening.

This research result and further analysis on the roles of adenosyl B12 and surrounding amino-acid residues could lead to the efficient production of useful materials by using adenosyl B12-dependent enzymes. In particular, diol dehydratase is considered to be a strong candidate for producing 1,3-propanediol from glycerol, a by-product obtained in bio-diesel fuel production from vegetable oils. 1,3-Propanediol is a monomer to synthesize polytrimethylene terephthalate that is a clothing fabric material known to be durable, highly elastic, and have a soft feel on the skin.

Figure: 1



Caption to Figure 1

Figure 1. Synchronized conformational change of the peripheral a-acetamide side chain of the corrin ring with the radical shuttling motion of an adenosyl radical between the original (left) and catalytic (right) positions. The hydrogen bonds of the a-side chain with the ribose 3´-OH group and with a certain active-site residue are crucial for maintaining the adenosyl radical in the appropriate position for efficient radical reaction. The a-side chain acts as a gate for the substrate channel of the enzymes as well.

Article Information

DOI: 10.1002/anie.201803591
Authors: Naoki Shibata, Yui Sueyoshi, Yoshiki Higuchi, Tetsuo Toraya
Journal: Angewandte Chemie International Edition
Title: Direct Participation of a Peripheral Side Chain of a Corrin Ring in Coenzyme B12 Catalysis
Year of Publication: 2018

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