Enzyme catalyzed radical dehydrations of hydroxy acids

Area of Science:

• Biochemistry
• Enzymology
• Radical biochemistry

Background:

• Radical biochemistry is increasingly dominated by S-adenosylmethionine (SAM) dependent enzymes.
• This review introduces 2- and 4-hydroxyacyl-CoA dehydratases, which utilize a novel radical generation mechanism.
• These enzymes form and recycle ketyl radicals via one-electron reduction/oxidation without additional energy input.

Purpose of the Study:

• To review four types of 2-hydroxyacyl-CoA dehydratases involved in amino acid fermentation by anaerobic bacteria.
• To elucidate the radical generation mechanism, including the identification of allylic ketyl radical intermediates.
• To present potential biotechnological applications of these radical dehydratases.

Main Methods:

• Focus on four types of 2-hydroxyacyl-CoA dehydratases from anaerobic bacteria, particularly clostridia.
• Enzyme activation via one-electron transfer from an iron-sulfur protein, driven by ATP hydrolysis.
• Elucidation of crystal structures for 2-hydroxyisocapryloyl-CoA dehydratase and 4-hydroxybutyryl-CoA dehydratase.

Main Results:

• Identification of the allylic ketyl radical intermediate in the reaction mechanism.
• Determination of crystal structures revealing conserved residues and stereochemistry.
• Demonstration of enzyme activation by an 'Archerase' mechanism involving electron transfer.

Conclusions:

• The 'Archerase' mechanism is an emerging principle in anaerobic metabolism.
• Radical dehydratases represent a distinct class of radical-generating enzymes.
• These dehydratases hold promise for biotechnological applications.