title: Insights into caerulomycin A biosynthesis: a two-component monooxygenase CrmH-catalyzed oxime formation.
abstract: The immunosuppressive agent caerulomycin A features a unique 2,2'-bipyridine core structure and an unusual oxime functionality. Genetic and biochemical evidence confirms that the oxime formation in caerulomycin A biosynthesis is catalyzed by CrmH, a flavin-dependent two-component monooxygenase that is compatible with multiple flavin reductases, from a primary amine via a N-hydroxylamine intermediate. Structure homologue-guided site-directed mutagenesis studies identify four amino acid residues that are essential for CrmH catalysis. This study provides the first biochemical evidence of a two-component monooxygenase that catalyzes oxime formation.
authors.affiliation: CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences , 164 West Xingang Road, Guangzhou 510301, P. R. China.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Zhang
authors.forename: Sumei
authors.initials: S
authors.lastname: Li
authors.forename: Qinheng
authors.initials: Q
authors.lastname: Lin
authors.forename: Peng
authors.initials: P
authors.lastname: Fu
authors.forename: Guangtao
authors.initials: G
authors.lastname: Zhang
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Shi
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhu
authors.forename: Changsheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D055162:Biocatalysis; D020134:Catalytic Domain; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010091:Oximes / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D010091:Oximes; D011725:Pyridines; C544423:caerulomycin A; D006899:Mixed Function Oxygenases