304
characterized by the presence of the unusual amino acids didehydroalanine (Dha)
and didehydrobutyrine (Dhb).
Lantibiotics are classified into Group A and Group B based on their molecular
weight, structure and biological activity. Type A lantibiotics (2.1–3.5 KDa, 21–38
amino acid residues) generally have a more linear secondary structure and are active
at nanomolar concentrations against gram-positive bacteria. They kill their targets
by forming pores in the cytoplasmic membrane. Type A lantibiotics produced by
Bacillus species include Subtilin (3320 Da) (Fig. 12.4a), which is a cationic, 32
amino acid pentacyclic lantibiotic produced by B. subtilis strain ATCC 6633. This
antimicrobial peptide is similar in its structure and mechanism of action to nisin, a
bacteriocin globally used as a food preservative (Gálvez et al. 2007). The peptide is
resistant to high acid and temperatures. It has a broad spectrum of activity against
many gram-positive bacteria, including Propionibacterium acnes (causative of skin
acne), Streptococci, Staphylococci and Clostridia. Subtilin binds to the cell wall
precursors lipid II and undecaprenyl pyrophosphate to form pores in the cell membrane and thereby cause antimicrobial activity (Parisot et al. 2008). Subtilin is biosynthesized from the structural gene SpaS which is a part of an operon-like structure
containing about ten genes involved in activation, regulation and cellular transport
of the gene product. Ericin S (3442 Da) and Ericin A (2986 Da) are two lantibioticlike peptides obtained from B. subtilis A1/3 produced from a gene cluster with high
degree of homology and occupying the same locus as the subtilisin gene cluster in
B. subtilis 6633. These peptides are active against many gram-positive bacteria,
including Clavibacter michiganensis, the causative organism for tomato bacterial
canker. Type B lantibiotics include globular and uncharged peptides. Mersacidin
(1825 Da) (Fig. 12.4b) produced by Bacillus sp. strain HIL Y-8554728 is a tetracyclic peptide lantibiotic belonging to this group. Mersacidin exhibits a globular
structure due to the presence of four intermolecular thioether bridges. They are
shown to have better protease resistance compared to other bacillus lantibiotics
owing to its structure. mersacidin” is active against methicillin-resistant S. aureus
(MRSA) and is similar to the glycopeptide vancomycin in its activity. It is also
active against vancomycin-resistant enterococci. Unlike type A lantibiotics, mersacidin inhibits cell wall biosynthesis instead of creating pores in the cell wall to
bring about its action. The biosynthetic gene cluster of mersacidin (12.3 kb) contains 10 open reading frames in addition to the mersacidin structural gene
mrsA. Apart from the structural genes, the cluster contains genes for precursor
modification enzymes (MrsM and MrsD) and a transport protein (MrsT). Screening
of genome sequence based on homology for lantibiotics resulted in the identification of a broad-spectrum two-peptide mersacidin-like lantibiotic called as lichenicidin (3020 Da) from B. licheniformis ATCC 14580 and another peptide (3250 Da)
with similar properties from B. licheniformis DSM 13. These peptides exhibit antimicrobial activity against methicillin-resistant S. aureus, Listeria monocytogenes
and vancomycin-resistant enterococci.
Subtilosin (Fig. 12.4c) and Sublancin 168 are peptides of Bacillus origin classified in a distinct group of lantibiotics due to their deviant structures. Subtilosin is an
anionic macrocyclic peptide antibiotic produced by B. subtilis and B.
D. Francis
characterized by the presence of the unusual amino acids didehydroalanine (Dha)
and didehydrobutyrine (Dhb).
Lantibiotics are classified into Group A and Group B based on their molecular
weight, structure and biological activity. Type A lantibiotics (2.1–3.5 KDa, 21–38
amino acid residues) generally have a more linear secondary structure and are active
at nanomolar concentrations against gram-positive bacteria. They kill their targets
by forming pores in the cytoplasmic membrane. Type A lantibiotics produced by
Bacillus species include Subtilin (3320 Da) (Fig. 12.4a), which is a cationic, 32
amino acid pentacyclic lantibiotic produced by B. subtilis strain ATCC 6633. This
antimicrobial peptide is similar in its structure and mechanism of action to nisin, a
bacteriocin globally used as a food preservative (Gálvez et al. 2007). The peptide is
resistant to high acid and temperatures. It has a broad spectrum of activity against
many gram-positive bacteria, including Propionibacterium acnes (causative of skin
acne), Streptococci, Staphylococci and Clostridia. Subtilin binds to the cell wall
precursors lipid II and undecaprenyl pyrophosphate to form pores in the cell membrane and thereby cause antimicrobial activity (Parisot et al. 2008). Subtilin is biosynthesized from the structural gene SpaS which is a part of an operon-like structure
containing about ten genes involved in activation, regulation and cellular transport
of the gene product. Ericin S (3442 Da) and Ericin A (2986 Da) are two lantibioticlike peptides obtained from B. subtilis A1/3 produced from a gene cluster with high
degree of homology and occupying the same locus as the subtilisin gene cluster in
B. subtilis 6633. These peptides are active against many gram-positive bacteria,
including Clavibacter michiganensis, the causative organism for tomato bacterial
canker. Type B lantibiotics include globular and uncharged peptides. Mersacidin
(1825 Da) (Fig. 12.4b) produced by Bacillus sp. strain HIL Y-8554728 is a tetracyclic peptide lantibiotic belonging to this group. Mersacidin exhibits a globular
structure due to the presence of four intermolecular thioether bridges. They are
shown to have better protease resistance compared to other bacillus lantibiotics
owing to its structure. mersacidin” is active against methicillin-resistant S. aureus
(MRSA) and is similar to the glycopeptide vancomycin in its activity. It is also
active against vancomycin-resistant enterococci. Unlike type A lantibiotics, mersacidin inhibits cell wall biosynthesis instead of creating pores in the cell wall to
bring about its action. The biosynthetic gene cluster of mersacidin (12.3 kb) contains 10 open reading frames in addition to the mersacidin structural gene
mrsA. Apart from the structural genes, the cluster contains genes for precursor
modification enzymes (MrsM and MrsD) and a transport protein (MrsT). Screening
of genome sequence based on homology for lantibiotics resulted in the identification of a broad-spectrum two-peptide mersacidin-like lantibiotic called as lichenicidin (3020 Da) from B. licheniformis ATCC 14580 and another peptide (3250 Da)
with similar properties from B. licheniformis DSM 13. These peptides exhibit antimicrobial activity against methicillin-resistant S. aureus, Listeria monocytogenes
and vancomycin-resistant enterococci.
Subtilosin (Fig. 12.4c) and Sublancin 168 are peptides of Bacillus origin classified in a distinct group of lantibiotics due to their deviant structures. Subtilosin is an
anionic macrocyclic peptide antibiotic produced by B. subtilis and B.
D. Francis