Methyl lanthionine

The regulation of bacteriocin synthesis by PPs goes back to mid-1990s when it was shown that the Class II bacteriocins (nonmodified heat-stable bacteriocins) as well as Class I bacteriocins most often referred to as lantibiotics (post-translatory modified containing most frequently lanthionine, methyl-lanthionine, dehydrated serine, and threonine) were regulated by small ribosomally synthesized peptides either resembling a peptide... 

Cinnamycin S. cinnamoneus Gram-pos. bacteria, acid-fast bacteria Are, Asp, GIu, Phe, Lanthionine, methyl-lanthionine, Pro, Val ... 

Lantibiotics are small, membrane-active peptides (< 5 kDa) containing the unusual amino acids lanthionine, P-methyl-lanthionine, and the dehydrated residues dehydro alanine and dehydrobutyrine e.g. nisin, lacticin 481, carnocin U-149, lactocin S, sublancin 168 [29-38]. The intrachain positioning of these polycyclic structures of the lantibiotics has been used to group them into linear (Group lA) or circular (Group IB) lantibiotics [39]. Based on similarities in the... 

Figure 11.2 Schematic representation of the structures of mature nisin. The molecule shown is nisin A, but the substitution of Asn27 for His27 in nisin Z is indicated. Dha is dehydroalanine, Dhb is dehydrobutyrine, Ala-S-Ala is lanthionine, and Abu-S-Ala is b-methyl-lanthionine. Reprinted from Cheigh, C.-I., Pyun, Y.-R., 2005. Nisin bios3mthesis and its properties.

A number of antibiotics contain amino acid residues that differ structurally from those found in proteins. Examples are ,y-diaminobutyric acid in the polymyxins, D- -aminoadipic acid in cephalosporin N and C, / -methyl-lanthionine in subtilin, nisin and cinnamycin, a-phenylsarcosine and L-a,lV-dimethylleucine in etamycin, (-)-)-, e-diamino-w-caproic acid ( 8-lysine) in streptothricini , and L-jS-methylaspartic acid (which can be formed from... 

Gross, E., and J. L. Morell Nisin. The Assignment of Sulfide Bridges of p-Methyl-lanthionine to a Novel Bicyclic Structure of Identical Ring Size. J. Amer. Chem. Soc. 92, 2919 (1970). 

Morell, j. L., P. Fleckenstein, and E. Gross Stereospecific Synthesis of (2S,3R)-2-Amino-3-mercaptobutyric Acid — an Intermediate for Incorporation into p-Methyl-lanthionine-Containing Peptides. J. Org. Chem. 42, 355 (1977). 

Dialkyl esters of cystine (39) and lanthionine (40) undergo a surprising thermolysis reaction at between 25 C and 80 °C to afford cis and trans methyl 2-methylthiazolidine-2,4-dicarboxylates (43) in protic solvents. A two stage process is proposed for this transformation. An initial i-elimination reaction gives the thiol (41) and the enamine (42). Thiol addition to the imine tautomer of (42) is then followed by loss of ammonia and an intramolecular cyclisation to give (43) <96CC843>. 

The use of Trt-protected 3-iodoalanines for lanthionine synthesis is also a highly promising method for the synthesis of 3-methyl- and 3,3-dimethyllanthionines. 40 This method is based on the use of A-trityl-3-iodoalanine benzyl ester (54) and the symmetrically protected bis(Boc)-cystine-derivative dimethyl esters derived from L-t/treo-3-methylcysteine and d-penicillamine. Yields of the respective lanthionine derivatives are >80% however, enantiomeric excesses have not been determined for the 3-substituted lanthionines (Scheme 18). 

Lantibiotics contain several unusual amino acids, including the thioether lanthionine (Lan) hnkage and its methyl substituted analog methyUanthionine (MeLan) (Fig. la) that unifies all members of the class and accounts for their family name. In addition to Lan, lantibiotics commonly contain 2,3-dehydroalanine (Dha) and (Z)-2,3-dehydrobutyrine (Dhb). In all, no less than 15 different posttranslational modifications have been documented in lantibiotics (for a selection see Fig. la), and up to 58% of their amino acids are modified. These extensive structmal alterations overcome the constraints imposed by the use of 20 amino acids in ribosomally synthesized peptides. Some less common, posttranslationally crafted residues in lantibiotics are fS-hydroxy aspartate, lysinoalanine, aminovinyl cysteine (AviCys), D-alanine, 2-oxobutyrate, 2-oxopropionate, and 2-hydroxypropionate. The presence of these unusual residues is thought to be important for the biological activity of lantibiotics. 

Methionine, methionine sulfoxide, methionine sulfone, S-methyl cysteine Cysteine, cystine, homocysteine, lanthionine, djenkolic acid Lanthionine, djenkolic acid... 

D-valine, A-methyl-L-valine, L-norvaline, L-y-formylmethylnorvaline L-ornithine, n-ornithine, IV-hydroxy-L-ornithine L-Ianthionine, 3-methyl-L-lanthionine... 

Additional common differences include demethylation of the amino acid residues 3 and/or 7 (41,78) whereby the dehydroalanine -variant was found to be 5-fold less toxic than the related methylated microcystin (39). Replacement of the Mdha residue with the precursor amino acid residue N-methyl-L-Ser is again minimally affecting the toxicity (34), but the variant with lanthionine in this position shows very weak toxicity probably due to the bulky modification (79). This indicates that the dehydro-amino acid residue itself is unimportant, a fact which is further supported by the observation that dihydro-microcystins, obtained by reduction of Mdha with sodium boron hydride, are hilly active both as the stereoisomeric mixture or as isolated isomers, i.e. microcystin-L-Ala and microcystin-D-Ala (80). 

Proteins, polypeptides, cystine, cysteine, glutathione Methionine, methionine sulfoxide, methionine sulfone, S-methyl cysteine Methionine, methionine sulfoxide, methionine sulfone, S-methyl cysteine, homocysteine Methionine, methionine sulfoxide, methionine sulfone, S-methyl cysteine Cysteine, cystine, homocysteine, lanthionine, djenkolic acid Lanthionine, djenkolic acid... 

Sulfur-containing amino acids related to cysteine and methionine are cysteic add and its decarboxylation product taurine. Lanthionine, with one sulfur atom less than cystine, has been isolated from wool hydrolyzates. Homocystdne is the de-methylation product of methionine. 

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