TY - JOUR
T1 - Effect of amino acid substitutions in conserved residues in the leader peptide on biosynthesis of the lantibiotic mutacin II
AU - Chen, Ping
AU - Qi, Feng Xia
AU - Novak, Jan
AU - Krull, Robert E.
AU - Caufield, Page W.
N1 - Funding Information:
This work was supported by NIH Grant DE09082. The mass spectrometer was purchased by funds from a NIH Instrumentation Grant (S10RR06487) and from UAB. Operation of the Mass Spectrometer Shared Facility has been supported in part by a NCI Core Research Support Grant to the UAB Comprehensive Cancer Center (P30 CA13148).
PY - 2001/2/20
Y1 - 2001/2/20
N2 - The lantibiotic mutacin II, produced by Streptococcus mutans T8, is a ribosomally synthesized peptide antibiotic that contains thioether amino acids such as lanthionine and methyllanthionine as a result of post-translational modifications. The mutacin II leader peptide sequence shares a number of identical amino acid residues with class AII lantibiotic leader peptides. To study the role of these conservative residues in the production of active antimicrobial mutacin, 15 mutations were generated by site-directed mutagenesis. The effects of these substitutions vary from no effect to complete block-out. Mutations G-1A, G-2A, I-4D, and L-7K completely blocked the production of mature mutacin. Other mutations (I-4V, L-7M, E-8D, S-11T/A, V-12I/A, and E-13D) had no detectable effect on mutacin production. The changes of Glu-8 to Lys, Val-12 to Leu, Glu-13 to Lys reduced the mutacin production level to about 75%, 50%, and 10% of the wild-type, respectively. Thus, our data indicated that some of these conserved residues are essential for the mutacin biosynthesis, whereas others are important for optimal biosynthesis rates.
AB - The lantibiotic mutacin II, produced by Streptococcus mutans T8, is a ribosomally synthesized peptide antibiotic that contains thioether amino acids such as lanthionine and methyllanthionine as a result of post-translational modifications. The mutacin II leader peptide sequence shares a number of identical amino acid residues with class AII lantibiotic leader peptides. To study the role of these conservative residues in the production of active antimicrobial mutacin, 15 mutations were generated by site-directed mutagenesis. The effects of these substitutions vary from no effect to complete block-out. Mutations G-1A, G-2A, I-4D, and L-7K completely blocked the production of mature mutacin. Other mutations (I-4V, L-7M, E-8D, S-11T/A, V-12I/A, and E-13D) had no detectable effect on mutacin production. The changes of Glu-8 to Lys, Val-12 to Leu, Glu-13 to Lys reduced the mutacin production level to about 75%, 50%, and 10% of the wild-type, respectively. Thus, our data indicated that some of these conserved residues are essential for the mutacin biosynthesis, whereas others are important for optimal biosynthesis rates.
KW - Lantibiotic
KW - Leader peptide
KW - Mutacin
KW - Mutagenesis
KW - Streptococcus
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U2 - 10.1016/S0378-1097(00)00565-6
DO - 10.1016/S0378-1097(00)00565-6
M3 - Article
C2 - 11179642
AN - SCOPUS:0035916407
SN - 0378-1097
VL - 195
SP - 139
EP - 144
JO - FEMS Microbiology Letters
JF - FEMS Microbiology Letters
IS - 2
ER -