Intriguing substrate tolerance of epoxide hydrolase Lsd19 involved in biosynthesis of the ionophore antibiotic lasalocid A.
Recently, we reported that the epoxide hydrolase Lsd19, the first enzyme shown to catalyze epoxide-opening cascades, can catalyze the conversion of a putative bisepoxide intermediate to polyether antibiotic lasalocid, which involves energetically disfavored 6-endo-tet cyclization of the epoxy alcohol. Here, we examined the substrate tolerance of Lsd19. Lsd19 accepts various substrate analogues differing in the left segment of lasalocid and epoxide stereochemistry to afford either THF-THP or THF-THF products with excellent regioselectivity.
Matsuura
Yusuke
Y
Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
Shichijo
Yoshihiro
Y
Minami
Atsushi
A
Migita
Akira
A
Oguri
Hiroki
H
Watanabe
Mami
M
Tokiwano
Tetsuo
T
Watanabe
Kenji
K
Oikawa
Hideaki
H
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D055162:Biocatalysis; D003500:Cyclization; D004851:Epoxide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D007832:Lasalocid / Q000096:biosynthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D004851:Epoxide Hydrolases; D007832:Lasalocid