Abstract
FR901459, a product of the fungus Stachybotrys chartarum No. 19392, is a derivative of cyclosporin A (CsA) and a powerful immunosuppressant that binds cyclophilin. Recently, it was reported that CsA was effective against hepatitis C virus (HCV). However, FR901459 lacks active moieties, which are essential for synthesizing more potent and safer derivatives of this anti-HCV agent. Here we identified an actinomycete strain (designated 7887) that was capable of efficient bioconversion of FR901459. Structural elucidation of the isolated bioconversion products (1-7) revealed that compounds 1-4 were mono-hydroxylated at the position of 1-MeBmt or 9-MeLeu, whereas compounds 5-7 were bis-hydroxylated at both positions. The results of morphological and chemical characterization, as well as phylogenetic analysis of 16S ribosomal DNA (rDNA), suggested that strain 7887 belonged to the genus Lentzea. Comparison of the FR901459 conversion activity of strain 7887 with several other Lentzea strains revealed that although all examined strains metabolized FR901459, strain 7887 had a characteristic profile with respect to bioconversion products. Taken together, these findings suggest that strain 7887 can be used to derivative FR901459 to produce a...Continue Reading
References
Nov 1, 1992·Applied Microbiology and Biotechnology·J SasakiS Omura
Oct 1, 1990·The Journal of Antibiotics·K NakagawaY Tsukamoto
Apr 1, 1995·International Journal of Systematic Bacteriology·A F YassinK P Schaal
Nov 11, 1994·Nucleic Acids Research·J D ThompsonT J Gibson
Mar 1, 1994·The Journal of Antibiotics·M SchulmanB Arison
Dec 1, 1993·The Journal of Antibiotics·K SakamotoM Okuhara
Sep 1, 1996·Clinical Immunology and Immunopathology·S HoG R Crabtree
Feb 25, 1999·Gastroenterology·T TakeuchiM Kohara
Jul 3, 1999·Science·V LohmannR Bartenschlager
Jun 20, 2001·International Journal of Systematic and Evolutionary Microbiology·D P LabedaT Tamura
Feb 6, 2002·The Journal of Antibiotics·R M HallN L Taylor
Jun 8, 2002·Biochemical and Biophysical Research Communications·Hiroe KishineKunitada Shimotohno
Jun 26, 2003·Journal of Gastroenterology·Kazuaki InoueMakoto Yoshiba
Oct 28, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Koichi WatashiKunitada Shimotohno
Sep 7, 2005·Gastroenterology·Mina NakagawaMamoru Watanabe
Jan 6, 2006·The Journal of Antibiotics·Motoo KobayashiHidenori Nakajima
Jul 1, 1948·Journal of Bacteriology·T G Pridham, D Gottlieb
Mar 30, 2007·Brain Research·Yuko MuramatsuNobuya Matsuoka
Sep 20, 1993·Biotechnology and Bioengineering·M HosobuchiH Yoshikawa
Jul 29, 2010·The Journal of Antibiotics·Satoshi SasamuraMichizane Hashimoto
Jul 15, 2011·Journal of Bioscience and Bioengineering·Satoshi UedaSeiji Hashimoto
Nov 28, 2012·Clinics in Liver Disease·Fernando E MembrenoEric J Lawitz
Dec 26, 2012·Bioorganic & Medicinal Chemistry·Isoko KuriyamaYoshiyuki Mizushina
Citations
Jun 30, 2016·The Journal of Antibiotics·Dominik WichnerMostafa E Rateb
Aug 23, 2016·Journal of Bioscience and Bioengineering·Tetsuya YabutaniHideo Nakano
Apr 14, 2017·Bioscience, Biotechnology, and Biochemistry·Tetsuya YabutaniHideo Nakano
Mar 23, 2017·Antonie van Leeuwenhoek·Hamidah IdrisMichael Goodfellow
May 3, 2020·The Journal of Antibiotics·Motoi UenoTakashi Shibata