In vivo conversion of L-serine to D-alanine in a ribosomally synthesized polypeptide.
In the course of characterizing the bacteriocin lactocin S and its encoding gene, we discovered three alanine-for-serine substitutions which, apparently, is a violation of the genetic code. Subsequent chiral analysis of lactocin S hydrolysates revealed a correlation between D-alanine content and the three substitutions, implying a conversion of L-serine to D-alanine in lactocin S maturation. In order to explain this observation, we suggest a sequence of events initiated by the dehydration of serine, which is common in the biosynthesis of the lanthionine-containing polycyclic lantibiotics (Schnell, N., Entian, K.-D., Schneider, U., Götz, F., Zähner, H., Kellner, R. & Jung, G. (1988) Nature 333, 276-278; Jung, G. (1991) Angew, Chem. Int. Ed. Engl. 30, 1051-1068; Bierbaum, G. & Sahl, H.-G. (1993) Zentralbl. Bakteriol. 278, 1-22) and completed by the stereospecific reduction of dehydroalanine residues. The occurrence of non-lanthionine alpha-carbon stereoinversion in lactocin S maturation substantiates the hypothetical alpha-epimerization scheme originally put forward by Bycroft (Bycroft, B. W. (1969) Nature 224, 595-597), and we propose a revision of this model to accommodate the lactocin S-type stereoinversion. Lactocin S is the first prokaryotic exception to the rule that only L-amino acids are included in ribosomally synthesized peptides.
Skaugen
M
M
Laboratory of Microbial Gene Technology, Agricultural University of Norway, As.
Nissen-Meyer
J
J
Jung
G
G
Stevanovic
S
S
Sletten
K
K
Inger
C
C
Abildgaard
M
M
Nes
I F
IF
D000409:Alanine / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000096:biosynthesis; D001430:Bacteriocins / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D003001:Cloning, Molecular; D007778:Lactobacillus / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D012270:Ribosomes / Q000378:metabolism; D012694:Serine / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism
D001426:Bacterial Proteins; D001430:Bacteriocins; D012694:Serine; C035728:lactocin; D000409:Alanine