371
15.2.7 Lariatins A and B
Lariatins A and B are antimycobacterial peptides isolated from cultures of
Rhodococcus jostii (Iwatsuki et al. 2007). Both the peptides have a lasso structure
(Fig. 15.1a) consisting of 18 and 20 amino acid residues, with the γ-carboxyl group
of Glu8 and the α-amino group of Gly1 forming an internal linkage giving the peptide its ring and tail appearance as depicted in Fig. 15.1b. Lariatins A and B were
isolated by the fermentation of a broth culture of R. jostii. The maximum production
of lariatin A was observed at day 10, whereas peak production of lariatin B was
observed by day 5. After fermentation, the broth was centrifuged to remove fungal
mycelia followed by sequential passage of supernatant and resulting eluates through
a series of columns. The active component was finally subjected to a preparative
HPLC with C18 column to obtain lariatin A at retention time of 44 min and lariatin
B at 56 min. The molecular formula of lariatin A is C 94 H 143 N 27 O 25 and B is
C 101 H 153 N 29 O 27 . Both lariatins inhibited the growth of M. smegmatis. In addition,
lariatin A also exhibited antimycobacterial activity against the virulent strain M.
tuberculosis, at ranges comparable to the first-line drug isoniazid, and the mechanism of action was postulated to be the inhibition of cell wall synthesis.
15.2.8 Lacticin 3147
Bacteriocin is a broad-range AMP with antimycobacterial activity isolated from
Lactococcus lactis subsp. lactis. Lacticin 3147 is a thermostable compound active
at pH 7.4. It is encoded by a 60.2 kDa plasmid. Lacticin 3147 forms pores in the cell
membrane of the target organism, thereby disrupting the membrane potential and
the pH gradient (Cotter et al. 2005; Carroll et al. 2012).
Gln
Ser
Leu
Val
Tyr
Arg
Lariatin
C
C
N Trp Val Gly His
Val Ile Lys R
Asn
Ser
H
C
O
O
A
R
Pro
Pro
Gly
Pro
B
O
NH
α
β
γ
HN
CH
CH 2
CH 2
( 8 Glu)
1 Gly
a
b
Fig. 15.1 (a) Lasso structure of lariatin A (Courtesy of Hiroshi Tomoda). (b) Structures of lariatins A and B (Courtesy of Hiroshi Tomoda)
15 Antimycobacterial Peptides
15.2.7 Lariatins A and B
Lariatins A and B are antimycobacterial peptides isolated from cultures of
Rhodococcus jostii (Iwatsuki et al. 2007). Both the peptides have a lasso structure
(Fig. 15.1a) consisting of 18 and 20 amino acid residues, with the γ-carboxyl group
of Glu8 and the α-amino group of Gly1 forming an internal linkage giving the peptide its ring and tail appearance as depicted in Fig. 15.1b. Lariatins A and B were
isolated by the fermentation of a broth culture of R. jostii. The maximum production
of lariatin A was observed at day 10, whereas peak production of lariatin B was
observed by day 5. After fermentation, the broth was centrifuged to remove fungal
mycelia followed by sequential passage of supernatant and resulting eluates through
a series of columns. The active component was finally subjected to a preparative
HPLC with C18 column to obtain lariatin A at retention time of 44 min and lariatin
B at 56 min. The molecular formula of lariatin A is C 94 H 143 N 27 O 25 and B is
C 101 H 153 N 29 O 27 . Both lariatins inhibited the growth of M. smegmatis. In addition,
lariatin A also exhibited antimycobacterial activity against the virulent strain M.
tuberculosis, at ranges comparable to the first-line drug isoniazid, and the mechanism of action was postulated to be the inhibition of cell wall synthesis.
15.2.8 Lacticin 3147
Bacteriocin is a broad-range AMP with antimycobacterial activity isolated from
Lactococcus lactis subsp. lactis. Lacticin 3147 is a thermostable compound active
at pH 7.4. It is encoded by a 60.2 kDa plasmid. Lacticin 3147 forms pores in the cell
membrane of the target organism, thereby disrupting the membrane potential and
the pH gradient (Cotter et al. 2005; Carroll et al. 2012).
Gln
Ser
Leu
Val
Tyr
Arg
Lariatin
C
C
N Trp Val Gly His
Val Ile Lys R
Asn
Ser
H
C
O
O
A
R
Pro
Pro
Gly
Pro
B
O
NH
α
β
γ
HN
CH
CH 2
CH 2
( 8 Glu)
1 Gly
a
b
Fig. 15.1 (a) Lasso structure of lariatin A (Courtesy of Hiroshi Tomoda). (b) Structures of lariatins A and B (Courtesy of Hiroshi Tomoda)
15 Antimycobacterial Peptides