Evidence for the role of the monB genes in polyether ring formation during monensin biosynthesis.
Ionophoric polyethers are produced by the exquisitely stereoselective oxidative cyclization of a linear polyketide, probably via a triepoxide intermediate. We report here that deletion of either or both of the monBI and monBII genes from the monensin biosynthetic gene cluster gave strains that produced, in place of monensins A and B, a mixture of C-3-demethylmonensins and a number of minor components, including C-9-epi-monensin A. All the minor components were efficiently converted into monensins by subsequent acid treatment. These data strongly suggest that epoxide ring opening and concomitant polyether ring formation are catalyzed by the MonB enzymes, rather than by the enzyme MonCII as previously thought. Consistent with this, homology modeling shows that the structure of MonB-type enzymes closely resembles the recently determined structure of limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis.
Gallimore
Andrew R
AR
Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom.
Stark
Christian B W
CB
Bhatt
Apoorva
A
Harvey
Barbara M
BM
Demydchuk
Yuliya
Y
Bolanos-Garcia
Victor
V
Fowler
Daniel J
DJ
Staunton
James
J
Leadlay
Peter F
PF
Spencer
Jonathan B
JB
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D004851:Epoxide Hydrolases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D005798:Genes, Bacterial; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008985:Monensin / Q000096:biosynthesis* / Q000737:chemistry*; D012240:Rhodococcus / Q000201:enzymology; D012542:Scattering, Radiation; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008985:Monensin; D004851:Epoxide Hydrolases; C115926:limonene-1,2-epoxide hydrolase