title: A comparative analysis of the sugar phosphate cyclase superfamily involved in primary and secondary metabolism.
abstract: Sugar phosphate cyclases (SPCs) catalyze the cyclization of sugar phosphates to produce a variety of cyclitol intermediates that serve as the building blocks of many primary metabolites, for example, aromatic amino acids, and clinically relevant secondary metabolites, for example, aminocyclitol/aminoglycoside and ansamycin antibiotics. Feeding experiments with isotopically labeled cyclitols revealed that cetoniacytone A, a unique C(7)N-aminocyclitol antibiotic isolated from an insect endophytic Actinomyces sp., is derived from 2-epi-5-epi-valiolone, a product of SPC. By using heterologous probes from the 2-epi-5-epi-valiolone synthase class of SPCs, an SPC homologue gene, cetA, was isolated from the cetoniacytone producer. cetA is closely related to BE-orf9 found in the BE-40644 biosynthetic gene cluster from Actinoplanes sp. strain A40644. Recombinant expression of cetA and BE-orf9 and biochemical characterization of the gene products confirmed their function as 2-epi-5-epi-valiolone synthases. Further phylogenetic analysis of SPC sequences revealed a new clade of SPCs that might regulate the biosynthesis of a novel set of secondary metabolites.
authors.affiliation: Genetics Program, College of Agricultural Sciences, Oregon State University, Corvallis, OR 97331-2212, USA.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Wu
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Flatt
authors.forename: Oliver
authors.initials: O
authors.lastname: Schlörke
authors.forename: Axel
authors.initials: A
authors.lastname: Zeeck
authors.forename: Tohru
authors.initials: T
authors.lastname: Dairi
authors.forename: Taifo
authors.initials: T
authors.lastname: Mahmud
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D003500:Cyclization; D003512:Cyclohexanones / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D013403:Sugar Phosphates / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D003512:Cyclohexanones; D013403:Sugar Phosphates; C466782:cetoniacytone A; D006026:Glycoside Hydrolases