title: Biocatalytic synthesis of pikromycin, methymycin, neomethymycin, novamethymycin, and ketomethymycin.
abstract: A biocatalytic platform that employs the final two monomodular type I polyketide synthases of the pikromycin pathway in vitro followed by direct appendage of D-desosamine and final C-H oxidation(s) in vivo was developed and applied toward the synthesis of a suite of 12- and 14-membered ring macrolide natural products. This methodology delivered both compound classes in 13 steps (longest linear sequence) from commercially available (R)-Roche ester in >10% overall yields.
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Hansen
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Rath
authors.forename: Eli B
authors.initials: EB
authors.lastname: Eisman
authors.forename: Alison R H
authors.initials: AR
authors.lastname: Narayan
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Kittendorf
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Mortison
authors.forename: Yeo Joon
authors.initials: YJ
authors.lastname: Yoon
authors.forename: David H
authors.initials: DH
authors.lastname: Sherman
mesh_terms: D055162:Biocatalysis; D001711:Biotransformation; D007783:Lactones / Q000378:metabolism; D018942:Macrolides / Q000138:chemical synthesis / Q000378:metabolism*; D048630:Polyketide Synthases / Q000378:metabolism
chemical_list: D007783:Lactones; D018942:Macrolides; C442771:novamethymycin; C008517:methymycin; C008594:neomethymycin; D048630:Polyketide Synthases; C003145:picromycin