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Published on: March 18, 2012
Menaquinone Biosynthesis: The Mechanism of 5,8-Dihydroxy-2-naphthoate Synthase (MqnD)
Hannah R Manion-Sommerhalter1, Dmytro Fedoseyenko1, Sumedh Joshi1
1Department of Chemistry, Texas A&M University, College Station, Texas 77842, United States.
Abstract:
MqnD catalyzes the conversion of cyclic dehypoxanthine futalosine (6) to 5,8-dihydroxy-2-naphthoic acid (7) and an uncharacterized product. This study describes a chemoenzymatic synthesis of 6. This synthesis achieved a 2-fold yield enhancement by using titanium(III) citrate as the reducing agent and another 5-fold yield enhancement using a fluorinated analogue of dehypoxanthine futalosine (5) that was converted to 6 by an ipso substitution mechanism. This synthetic route enabled the synthesis of 6 in sufficient quantity to identify the second reaction product and to determine that the MqnD-catalyzed reaction proceeds by a hemiacetal ring opening-tautomerization-retroaldol sequence.
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