1. KUVEMPU UNIVERSITY
Sahyadri Science College, Shivamogga
Department of PG Studies and Research in Biotechnology
Under the Supervision of
Dr. Lakshminarayana T S
Dept of PG Studies and Research in Biotechnology
Sahyadri Science College,
Shivamogga
Submitted by:
Mr. Ganapati Yadav
M.Sc. II Year (Biotechnology)
Sahyadri Science College
Shivamogga
SEMINAR TOPIC
ON
“ LANTIBIOTICS”
2. INTRODUCTION
Lantibiotics are the lanthionine containing peptide antibiotics.
They are produced by a large number of Gram +ve bacteria such
as Streptococcus and Streptomyces.
Size ranging from 19 to 38 amino acids.
Lantibiotics – Bacteriocins
1. Class I (Lantibiotics)
2. Class II (Unmodified peptides)
3. Class III (Heat-labile peptides)
4. Class IV (Cyclic peptides)
Commercial uses –
Food industry for food preservation and making cheese
Veterinary antibiotics
Clinical antibiotics
Structures of lantibiotic’s
3. HISTORY
The name lantibiotics was introduced in 1988 as an abbreviation
for “lanthionine-containing peptide antibiotics”.
The first structures of these antimicrobial agents were produced
by pioneering work by Gross and Morell in the late 1960s
4. DEFINITION
Lantibiotics are gene-encoded peptides that contain
intramolecular ring structures, introduced through the
thioether containing lanthionine and methyllanthionine
residues.
The overwhelming majority of them shows antibacterial
activity.
Example:
• Nisin and epidermin are members of a family of
lantibiotics that bind to lipid II, a cell wall precursor lipid
component of target bacteria and disrupt cell wall
production.
• The duramycin family of lantibiotics binds
phosphoethanolamine in the membranes of its target cells
and seem to disrupt several physiological functions.
5. CLASSIFICATION
Type A lantibiotics are long flexible molecules
e.g., nisin, bisin, subtilin, epidermin, gallidermin
Subgroup AI includes mutacin II;
subgroup AII includes mutacin I and III.
Type B lantibiotics are globular
e.g., mersacidin,actagardine, duramycin, and cinnamycin.
Type C Some contain 2 peptides
e.g. haloduracin.
7. BIOSYNTHESIS
They are synthesized with a leader polypeptide sequence that is removed only during the transport of the molecule out
of the synthesizing cell.
Lantibiotics are expressed as prepropeptides, with an N-terminal leader sequence and a C-terminal propeptide part,
which is posttranslationally modified.
Biosynthesis starts with enzymatic dehydration of serine and/or threonine residues in the propeptide part yielding the
unusual amino acids 2,3-dehydroalanine (Dha) and 2,3-dehydrobutyrine (Dhb).
To some of these dehydroamino acids, the thiol group of a neighbouring cysteine residue is added resulting in the
characteristic meso-lanthionine (from Dha) and threo- ß-lanthionine (from Dhb) residues.
There are four known enzymes (lanthipeptide synthetases) responsible for producing lanthionine rings.
The modifications are introduced by one biosynthetic enzyme (LanM) or a combination of a dehydratase (LanB) and a
cyclase (LanC).
Fig: General mechanism for the formation of the thioether Lan during lantibiotic maturation
8. MECHANISM OF ACTION
Lantibiotics show substantial specificity for some components (e.g., lipid II) of bacterial cell membranes especially of Gram-
positive bacteria.
Type A lantibiotics kill rapidly by pore formation, type B lantibiotics inhibit peptidoglycan biosynthesis.
They are active in very low concentrations.
These peptides form a complex with the ultimate cell wall precursor lipid II, thereby inhibiting cell wall biosynthesis.
The complexes then aggregate, incorporate further peptides and form a pore in the bacterial membrane.
Complexing of lipid II is widespread among lantibiotics; however, pore formation depends on the overall length of the peptide
and the lipid composition of the test strain membrane.
9. APPLICATION
Food preservation
• Lantibiotics are produced by Gram-positive bacteria
and show strong antimicrobial action toward a wide
range of other Gram-positive bacteria.
• Nisin is used for the food preservation (by inhibiting
pathogens that cause food spoilage) and the
pharmaceutical industry (to prevent or fight
infections in humans or animals).
10. Veterinary antibiotic
•Duramycin is used for chickens.
Clinical antibiotic
•One type known as B lantibiotic NVB302 reported good results for use against Clostridium difficile.
Treatment:
•To treat inflammation, allergies, skin infections, peptic ulcers, etc.
11. LANTIBIOTICS COMMERCIALY RELAVENT
TARGET
INVIVO
TESTS
POTENTIALAPPLICATIONS
Nisin Gram positive bacteria Treatment of staphylococcal (including MRSA) and
enterococcal infections. Treatment of bacterial mastitis.
Oral hygiene, deodorants. Anticancer
mersacidin MRSA VRE, C.difficile Treatment of staphylococcal (including MRSA) and
enterococcal infections. Treatment of CDAD
Actagardine MRSA, VRE, C.difficile Treatment of staphylococcal ( including MRSA) and
enterococcal infections. Treatment of CDAD
Deoxyactagardine/ NVB302 C. difficile Treatment of C. difficile infection
Galidermin/ Epidermin Propinobacteria, staphylococci, streptococci Skin disorders including acne, eczerna, folic ulitis and
impetigo
Pinensins Yeast/ fungi Antifungal/ yeast
planosporicin MRSA, VRE, Streptococci Treatment of staphylococcal ( including MRSA) and
enterococcal infections including VRE
Microbisporicin MRSA, VISA, VRE, C. difficile Treatment of staphylococcal ( including MRSA and
VISA) and enterococcal infection including VRE, Acne
Mutasim B Ny266 Multi – drug resistant bacteria Treatment of multi – drug resistant bacteria including
MRSA and VRE
Lacticine 3147 Gram positive bacteria Treatment of bacterial mastitis, staphylococcal and
enterococcal infections including VRE and Acne
Saliviricin B Streptococci including S.pyogenes and
S.sobrinus
Treatment of streptococcal infections with emphasis on
the causative agents of sore throat
Duramycin Increase chloride transport and fluid Treatment of cystic fibrosis, ocular diseases and disorder
Applications of lantibiotics
12.
13. REFERENCE
• Chatterjee C, Paul M, Xie L, van der Donk WA (February 2005). "Biosynthesis and mode of action of
lantibiotics". Chem. Rev. 105 (2): 633–84.
• Jack, R.W. and Sahl, H.-G. (1995) “Unique peptide modifcations involved in the biosynthesis of lantibiotics”.
Trends. Biotechnol. 13, 269-278.
• Kellner R, Jung G, Horner T, Zahner H, Schnell N, Entian KD, Gotz F (October 1988). "Gallidermin: a new
lanthionine-containing polypeptide antibiotic". Eur. J. Biochem. 177 (1): 53–9.
• Siegers K, Heinzmann S, Entian KD (May 1996). "Biosynthesis of lantibiotic nisin. Posttranslational
modification of its prepeptide occurs at a multimeric membrane-associated lanthionine synthetase
complex". J. Biol. Chem. 271 (21): 12294–301.