title: Incorporation of nonmethyl branches by isoprenoid-like logic: multiple beta-alkylation events in the biosynthesis of myxovirescin A1.
abstract: Several polyketide secondary metabolites are predicted to undergo isoprenoid-like beta-alkylations during biosynthesis. One such secondary metabolite is myxovirescin A1, produced by Myxococcus xanthus. Myxovirescin is of special interest in that it appears to undergo two distinct beta-alkylations. Additionally, the myxovirescin biosynthetic gene cluster lacks tandem thiolation domains required in the synthesis of other beta-branched secondary metabolites. To probe the origins of the beta-branches in myxovirescin, we heterologously overexpressed the proteins predicted to be responsible for myxovirescin beta-alkylation and reconstituted their activities in vitro on model substrates. Our results confirm that myxovirescin undergoes two isoprenoid-like beta-alkylations during its biosynthesis, including an unprecedented beta-ethylation. The study of its biosynthesis should shed light on the scope and requirements for isoprenoid-like biosynthetic logic in a polyketide context.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Calderone
authors.forename: David F
authors.initials: DF
authors.lastname: Iwig
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
authors.forename: Neil L
authors.initials: NL
authors.lastname: Kelleher
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Walsh
mesh_terms: D000478:Alkylation; D004591:Electrophoresis, Polyacrylamide Gel; D005583:Fourier Analysis; D007783:Lactones / Q000378:metabolism; D013058:Mass Spectrometry; D013729:Terpenes / Q000378:metabolism*
chemical_list: D007783:Lactones; D013729:Terpenes; C036969:myxovirescin A