Incorporation of nonmethyl branches by isoprenoid-like logic: multiple beta-alkylation events in the biosynthesis of myxovirescin A1.
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.
Calderone
Christopher T
CT
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Iwig
David F
DF
Dorrestein
Pieter C
PC
Kelleher
Neil L
NL
Walsh
Christopher T
CT
D000478:Alkylation; D004591:Electrophoresis, Polyacrylamide Gel; D005583:Fourier Analysis; D007783:Lactones / Q000378:metabolism; D013058:Mass Spectrometry; D013729:Terpenes / Q000378:metabolism*
D007783:Lactones; D013729:Terpenes; C036969:myxovirescin A