title: Spirohexalines, new inhibitors of bacterial undecaprenyl pyrophosphate synthase, produced by Penicillium brasilianum FKI-3368.
abstract: An enzyme assay for bacterial undecaprenyl pyrophosphate (UPP) synthase was performed to screen microbial culture broths for inhibitors of UPP synthase. During the course of this screening program, an EtOH extract of a rice culture of Penicillium brasilianum FKI-3368 was found to inhibit UPP synthase activity. From activity-guided purification, a new compound-designated spirohexaline was isolated together with the structurally related and known viridicatumtoxin by ethyl acetate extraction silica gel and octadecylsilane column chromatographies and high-performance liquid chromatography. The structure of spirohexaline was elucidated by spectroscopic analysis, including NMR. Spirohexaline and viridicatumtoxin have a common hexacycline structure produced by fusion of a tetracycline-type ring with a spiro-type ring. They inhibited UPP synthase activity with IC₅₀ values of 9.0 and 4.0 μM, respectively.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Inokoshi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Zhang
authors.initials: Z
authors.lastname: Hongbin
authors.forename: Ryuji
authors.initials: R
authors.lastname: Uchida
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nonaka
authors.forename: Rokuro
authors.initials: R
authors.lastname: Masuma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D009183:Mycotoxins / Q000494:pharmacology*; D010407:Penicillium / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D009183:Mycotoxins; D013141:Spiro Compounds; C573901:spirohexaline; D019883:Alkyl and Aryl Transferases; C023266:undecaprenyl pyrophosphate synthetase