title: Engineered biosynthesis of hybrid macrolide polyketides containing D-angolosamine and D-mycaminose moieties.
abstract: The glycosylation of natural product scaffolds with highly modified deoxysugars is often essential for their biological activity, being responsible for specific contacts to molecular targets and significantly affecting their pharmacokinetic properties. In order to provide tools for the targeted alteration of natural product glycosylation patterns, significant strides have been made to understand the biosynthesis of activated deoxysugars and their transfer. We report here efforts towards the production of plasmid-borne biosynthetic gene cassettes capable of producing TDP-activated forms of D-mycaminose, D-angolosamine and D-desosamine. We additionally describe the transfer of these deoxysugars to macrolide aglycones using the glycosyl transferases EryCIII, TylMII and AngMII, which display usefully broad substrate tolerance.
authors.affiliation: Biotica Technology Ltd, Chesterford Research Park, Little Chesterford, Saffron Walden, Essex, CB10 1XL, UK.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schell
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Haydock
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Kaja
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carletti
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Lill
authors.forename: Eliot
authors.initials: E
authors.lastname: Read
authors.forename: Lesley S
authors.initials: LS
authors.lastname: Sheehan
authors.forename: Lindsey
authors.initials: L
authors.lastname: Low
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Fernandez
authors.forename: Friederike
authors.initials: F
authors.lastname: Grolle
authors.forename: Hamish A I
authors.initials: HA
authors.lastname: McArthur
authors.forename: Rose M
authors.initials: RM
authors.lastname: Sheridan
authors.forename: Peter F
authors.initials: PF
authors.lastname: Leadlay
authors.forename: Barrie
authors.initials: B
authors.lastname: Wilkinson
authors.forename: Sabine
authors.initials: S
authors.lastname: Gaisser
mesh_terms: D003001:Cloning, Molecular; D005818:Genetic Engineering; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D018942:Macrolides / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D005810:Multigene Family / Q000235:genetics; D017421:Sequence Analysis; D013302:Streptomyces / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C532512:D-angolosamine; D018942:Macrolides; C013610:mycaminose; D005944:Glucosamine