biostudies-literatureCalderone CTNIAID NIH HHSNIGMS NIH HHS835-46https://www.ebi.ac.uk/biostudies/studies/S-EPMC2084360biostudies-literatureUnknown14(7)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, Chemistry & biologyIncorporation of nonmethyl branches by isoprenoid-like logic: multiple beta-alkylation events in the biosynthesis of myxovirescin A1.PMC2084360GM067725GM073323AI042738R01 AI042738F32 GM020011F32 GM073323GM020011GM081743R01 GM020011F32 GM081743R01 GM067725Iwig DFWalsh CTDorrestein PCKelleher NLCalderone CTfalseIncorporation 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, 2007-01-01T00:00:00Z2007 Jul2026-05-02T20:53:36.607Z2019-03-27T02:22:00ZS-EPMC20843601765632010.1016/j.chembiol.2007.06.008