title: Bioconversion of AS1387392: screening and characterization of actinomycetes that convert AS1387392 to AS1429716.
abstract: AS1387392 was a novel and powerful histone deacetylase inhibitor with an excellent oral absorption profile, but this compound was lacking in active moieties, which are essential to synthesize more derivatives. In our screening program to identify actinomycetes capable of converting AS1387392 to AS1429716, which has an active moiety to synthesize more derivatives, we identified 12 strains capable of efficient hydroxylation. Results of phylogenetic analysis of 16S rDNA sequences suggested that these strains belonged to the genera Lentzea, Saccharopolyspora, Sphaerisporangium and Amycolatopsis. Morphological and chemical characteristics as well as results of phylogenetic analysis suggested that strain No. 7980 was a new species belonging to the genus Amycolatopsis, according to the FASTA search result of 16S rDNA gene sequence. Using these strains, we can easily produce AS1429716 as a chemical template for further chemical modifications, which may provide more effective and safer immunosuppressant.
authors.affiliation: Pharmacology Research Laboratories, Astellas Pharma, Ibaraki, Japan. satoshi.sasamura@jp.astellas.com
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasamura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Takase
authors.forename: Akihiko
authors.initials: A
authors.lastname: Fujie
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujii
authors.forename: Motohiro
authors.initials: M
authors.lastname: Hino
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Michizane
authors.initials: M
authors.lastname: Hashimoto
mesh_terms: D039903:Actinobacteria / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000737:chemistry; D004275:DNA, Ribosomal / Q000737:chemistry*; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism*; D010802:Phylogeny; D013045:Species Specificity
chemical_list: C554554:AS 1387392; C554555:AS 1429716; D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D056572:Histone Deacetylase Inhibitors; D007166:Immunosuppressive Agents; D010456:Peptides, Cyclic