FR177391, a new anti-hyperlipidemic agent from Serratia. III. Microbial conversion of FR177391 and synthesis of FR177391 derivatives for its target protein screening by chemical genetic approaches.
FR177391 produced by Serratia liquefaciens No. 1821 enhances differentiation of mouse 3T3-L1 fibroblasts to adipocytes and reduces the circulating levels of triglyceride in C57BL/KsJ-db/bd mice, an obese non-insulin-dependent diabetes mellitus animal model, although its mechanism of actions remained to be unknown. Its active derivative, 20-hydroxy FR177391, and its inactive derivative, 3-hydroxy FR177391 were produced by microbial conversion of FR177391, and biotin-labeled FR177391 was synthesized from 20-hydroxy FR177391 as an active affinity ligand to identify target molecules of FR177391 by chemical genetic approaches.
Kobayashi
Motoo
M
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co Ltd, Tsukuba, Ibaraki, Japan. motoo.kobayashi@jp.astellas.com
Sato
Kentaro
K
Yoshimura
Seiji
S
Yamaoka
Makiko
M
Takase
Shigehiro
S
Ohkubo
Mitsuru
M
Fujii
Takashi
T
Nakajima
Hidenori
H
D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D012705:Serratia / Q000737:chemistry*
D000960:Hypolipidemic Agents