TY - JOUR
T1 - Discovery of a single monooxygenase that catalyzes carbamate formation and ring contraction in the biosynthesis of the legonmycins
AU - Huang, Sheng
AU - Tabudravu, Jioji
AU - Elsayed, Somayah S.
AU - Travert, Jeanne
AU - Peace, Doe
AU - Tong, Ming Him
AU - Kyeremeh, Kwaku
AU - Kelly, Sharon M.
AU - Trembleau, Laurent
AU - Ebel, Rainer
AU - Jaspars, Marcel
AU - Yu, Yi
AU - Deng, Hai
N1 - Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. The discovery and characterization of the multifunctional FAD-dependent enzyme LgnC is now described. The enzyme is shown to convert indolizidine intermediates into pyrrolizidines through an unusual ring expansion/contraction mechanism, and catalyze the biosynthesis of new bacterial PAs, the so-called legonmycins. By genome-driven analysis, heterologous expression, and gene inactivation, the legonmycins were also shown to originate from non-ribosomal peptide synthetases (NRPSs). The biosynthetic origin of bacterial PAs has thus been disclosed for the first time. Solo performance: The legonmycins, new bacterial pyrrolizidine alkaloids, are assembled by a non-ribosomal peptide synthetase. The multifunctional FAD-containing enzyme LgnC catalyzes the transformation of indolizidine intermediates into pyrrolizidines by carbamate formation, followed by hydrolysis, decarboxylation-driven ring contraction, and hydroxylation as the crucial steps of legonmycin biosynthesis.
AB - Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. The discovery and characterization of the multifunctional FAD-dependent enzyme LgnC is now described. The enzyme is shown to convert indolizidine intermediates into pyrrolizidines through an unusual ring expansion/contraction mechanism, and catalyze the biosynthesis of new bacterial PAs, the so-called legonmycins. By genome-driven analysis, heterologous expression, and gene inactivation, the legonmycins were also shown to originate from non-ribosomal peptide synthetases (NRPSs). The biosynthetic origin of bacterial PAs has thus been disclosed for the first time. Solo performance: The legonmycins, new bacterial pyrrolizidine alkaloids, are assembled by a non-ribosomal peptide synthetase. The multifunctional FAD-containing enzyme LgnC catalyzes the transformation of indolizidine intermediates into pyrrolizidines by carbamate formation, followed by hydrolysis, decarboxylation-driven ring contraction, and hydroxylation as the crucial steps of legonmycin biosynthesis.
KW - biosynthesis
KW - legonmycins
KW - multifunctional enzymes
KW - non-ribosomal peptide synthetases
KW - pyrrolizidine alkaloids
UR - http://www.scopus.com/inward/record.url?scp=84944279359&partnerID=8YFLogxK
U2 - 10.1002/anie.201502902
DO - 10.1002/anie.201502902
M3 - Article
C2 - 26206556
AN - SCOPUS:84944279359
SN - 1433-7851
VL - 54
SP - 12697
EP - 12701
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 43
ER -