Lacticin 481: in vitro reconstitution of lantibiotic synthetase activity.
The lantibiotic lacticin 481 is synthesized on ribosomes as a prepeptide (LctA) and posttranslationally modified to its mature form. These modifications include dehydration of serines and threonines, followed by intramolecular addition of cysteines to the unsaturated amino acids, which generates cyclic thioethers. This process breaks eight chemical bonds and forms six newbonds and is catalyzed by one enzyme, LctM. We have characterized the in vitro activity of LctM, which completely processed a series of LctA mutants, displaying a permissive substrate specificity that holds promise for antibiotic engineering.
Xie
Lili
L
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL61801, USA.
Miller
Leah M
LM
Chatterjee
Champak
C
Averin
Olga
O
Kelleher
Neil L
NL
van der Donk
Wilfred A
WA
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D001430:Bacteriocins; D003001:Cloning, Molecular; D003545:Cysteine / Q000378:metabolism; D004798:Enzymes / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D013294:Lactococcus lactis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012694:Serine / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity; D013912:Threonine / Q000378:metabolism
D001426:Bacterial Proteins; D001430:Bacteriocins; D004798:Enzymes; C481644:LctM protein, Lactococcus lactis; D011498:Protein Precursors; C082508:lacticin 481; D013912:Threonine; D012694:Serine; D003545:Cysteine