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Title page for ETD etd-12052012-152927


Type of Document Dissertation
Author Al-Mestarihi, Ahmad H
Author's Email Address ahmad.h.al-mestarihi@vanderbilt.edu
URN etd-12052012-152927
Title Oxidation of deoxyaminosugars by a new flavin-dependent monooxygenase
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
Brian O. Bachmann Committee Chair
Michael P. Stone Committee Member
Richard N. Armstrong Committee Member
Tina M. Iverson Committee Member
Keywords
  • Everninomicin
  • Baumycin
  • DnmZ
  • Monooxygenase
  • Nitrososynthase
  • Deoxysugars
Date of Defense 2012-10-16
Availability unrestricted
Abstract
This research work aims to provide biochemical characterization of the enzyme(s) responsible for deoxyaminosugar oxidation in several glycosylated natural products. The enzyme homologues ORF36 and RubN8 from the everninomicn and the rubradirin biosynthetic pathways, respectively, were shown to catalyze amine to nitroso oxidation of the deoxyaminosugar TDP-L-epi-vancosamine. Catalysis was shown to proceed through two FAD/NADPH-dependent monooxygenation steps in which the aminosugar is first oxidized to the corresponding hydroxylamine, followed by a second N-oxygenation to form the nitrososugar. Intrestingly, DnmZ, a nitrososynthase homologue from Streptomyces peucetius, was shown to mediate a subsequent carbon-carbon bond cleavage of the formed β-hydroxy-nitrososugar. This retro-aldol activity represents a new and important addition to the functions known for flavin-dependent monooxygenases and expands our knowledge into late steps of baumycin biosynthesis.
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