ponent contains two potential ATP-binding consensus sites [104]. The proteins
encoded by these operons resemble the E. coli MalFGK2 and HisMQP2 transporters [163–165] and the SpaFG and McbFE proteins, which are involved in
immunity against subtilin [110] and microcin B17 [109], respectively. The
hydrophobicity plot of NisF and NisE together resembles that of the complete
SpaF protein [104]. It was therefore proposed that NisF and NisE constitute the
transmembrane and ATP-binding domains of an ATP-dependent translocator
[104]. Based on homologies with colicin immunity proteins, NisG was predicted
to have a similar function in nisin immunity [104]. In the case of epidermin,
EpiE and EpiG were, based on mutual homology, both predicted as ABC transporter membrane components with six potential membrane-spanning helices,
a common feature of these transporter systems [163]. EpiEGF2 were therefore
thought to act as a hetero-tetrameric complex, including EpiG, in comparison
with the well-characterized MalFGK2 and HisMQP2 transporters [163–165]
but in contradiction with the postulated function for NisG [104]. Immunity
conferred by this ABC secretory system could be mediated by active extrusion
or by their uptake and intracellular degradation [104, 163].
A gene, nsr, conferring resistance against nisin has been isolated from L.
lactis subsp. lactis biovar diacetylactis DRC5, which is a nisin-nonproducer
[166, 167]. Nsr is a 318-amino acid residue protein with a hydrophobic N-terminus, resulting in membrane association. The level of resistance conferred by
Nsr was only 10% of the immunity of the nisin producer strain [107]. The nsr
gene did not hybridize with genomic DNA of the nisin producer strain L. lactis
subsp. lactis ATCC 11454, demonstrating that the genetic determinants for
immunity and resistance are different, as are their expected mechanisms of
action [167]. Although nisin resistance has been reported among a variety of
Gram-positive bacteria [34], in the only case studied up to now, B. cereus
produced a nisin reductase that presumably inactivated one or more of the
dehydroresidues required for nisin activity [168, 169].
5
Biosynthesis of Bacteriocins Produced by Lactic Acid Bacteria
5.1
Response Regulation
Many of the bacterial metabolic pathways are induced by various extracellular
stimuli. Those environmental conditions are sensed and signaled through, by
means of signal transduction systems. Many of these systems consist of two
components, a sensor, often located in the cytoplasmic membrane and a
cytoplasmic response regulator [108, 170–172]. They are therefore generally
called two-component systems. The environmental sensor acts as a histidine
protein kinase (HPK) and modifies the response regulator (RR) protein, which
in turn triggers an adapting response, in most cases by gene regulation. Most
histidine protein kinases consist of an N-terminal sensory domain and a
cytoplasmic C-terminal transmitter. The latter contains an autokinase domain
and a conserved histidine residue as a site for phosphorylation. Both domains
38
E. Sablon et al.
encoded by these operons resemble the E. coli MalFGK2 and HisMQP2 transporters [163–165] and the SpaFG and McbFE proteins, which are involved in
immunity against subtilin [110] and microcin B17 [109], respectively. The
hydrophobicity plot of NisF and NisE together resembles that of the complete
SpaF protein [104]. It was therefore proposed that NisF and NisE constitute the
transmembrane and ATP-binding domains of an ATP-dependent translocator
[104]. Based on homologies with colicin immunity proteins, NisG was predicted
to have a similar function in nisin immunity [104]. In the case of epidermin,
EpiE and EpiG were, based on mutual homology, both predicted as ABC transporter membrane components with six potential membrane-spanning helices,
a common feature of these transporter systems [163]. EpiEGF2 were therefore
thought to act as a hetero-tetrameric complex, including EpiG, in comparison
with the well-characterized MalFGK2 and HisMQP2 transporters [163–165]
but in contradiction with the postulated function for NisG [104]. Immunity
conferred by this ABC secretory system could be mediated by active extrusion
or by their uptake and intracellular degradation [104, 163].
A gene, nsr, conferring resistance against nisin has been isolated from L.
lactis subsp. lactis biovar diacetylactis DRC5, which is a nisin-nonproducer
[166, 167]. Nsr is a 318-amino acid residue protein with a hydrophobic N-terminus, resulting in membrane association. The level of resistance conferred by
Nsr was only 10% of the immunity of the nisin producer strain [107]. The nsr
gene did not hybridize with genomic DNA of the nisin producer strain L. lactis
subsp. lactis ATCC 11454, demonstrating that the genetic determinants for
immunity and resistance are different, as are their expected mechanisms of
action [167]. Although nisin resistance has been reported among a variety of
Gram-positive bacteria [34], in the only case studied up to now, B. cereus
produced a nisin reductase that presumably inactivated one or more of the
dehydroresidues required for nisin activity [168, 169].
5
Biosynthesis of Bacteriocins Produced by Lactic Acid Bacteria
5.1
Response Regulation
Many of the bacterial metabolic pathways are induced by various extracellular
stimuli. Those environmental conditions are sensed and signaled through, by
means of signal transduction systems. Many of these systems consist of two
components, a sensor, often located in the cytoplasmic membrane and a
cytoplasmic response regulator [108, 170–172]. They are therefore generally
called two-component systems. The environmental sensor acts as a histidine
protein kinase (HPK) and modifies the response regulator (RR) protein, which
in turn triggers an adapting response, in most cases by gene regulation. Most
histidine protein kinases consist of an N-terminal sensory domain and a
cytoplasmic C-terminal transmitter. The latter contains an autokinase domain
and a conserved histidine residue as a site for phosphorylation. Both domains
38
E. Sablon et al.