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9.B.351.  The Lantibiotic Immunity Protein (LIP) Family

Lantibiotics are antimicrobial peptides from the bacteriocin family, secreted by Gram-positive bacteria. These peptides differ from other bacteriocins by the presence of (methyl)lanthionine residues, which result from enzymatic modification of precursor peptides encoded by structural genes. Several groups of lantibiotics have been distinguished, the largest of which is the lacticin 481 group. This group consists of many members, including lacticin 481, streptococcin A-FF22, mutacin II, nukacin ISK-1, and salivaricins. Dufour et al. 2007 reviewed this lantibiotic group. They discussed the transcriptional regulation of the lantibiotic genes, the biosynthetic machinery, in particular the ability to perform in vitro prepeptide maturation, and partial characterization of the type of immunity protein used. This group differs in many aspects from the best known lantibiotic group (the nisin group), but shares properties with less-studied groups such as the mersacidin, cytolysin and lactocin S groups.

Immunity to a lantibiotic, nukacin ISK-1, is conferred by NukFEG (ABC transporter) and NukH (lantibiotic-binding protein) cooperatively. Okuda et al. 2005 identified the functional domains of NukH. The topological analysis indicated that NukH possesses two external loops and three TMSs. Deletion of the N or C terminus of NukH did not affect its function, but amino acid substitutions in the respective loops abolished function. Deletion of the third TMS also resulted in loss of immunity but did not affect the binding activity. These findings suggest that the whole structure of NukH, except for the N- and C-termini, is essential for its full immunity function, and that NukH somehow inactivates nukacin ISK-1 after binding. Recombinant L. lactis expressing nukH interacted with nukacin ISK-1 and lacticin 481 but not with nisin A (Aso et al. 2005). NukH recognizes the C-terminal ring region of nukacin ISK-1 in an energy-independent fashon. Thus, after being captured by NukH in an energy-independent manner, nukacin ISK-1 is transported out by NukFEG in an energy-dependent manner (Okuda et al. 2008). Unusual amino acids play a role in NukH recognition, and nukacin may bind to NukH via an intermolecular disulfide bond after it is weakly recognized by NukH (Okuda et al. 2008).

References associated with 9.B.351 family:

Aso, Y., K. Okuda, J. Nagao, Y. Kanemasa, N. Thi Bich Phuong, H. Koga, K. Shioya, T. Sashihara, J. Nakayama, and K. Sonomoto. (2005). A novel type of immunity protein, NukH, for the lantibiotic nukacin ISK-1 produced by Staphylococcus warneri ISK-1. Biosci. Biotechnol. Biochem. 69: 1403-1410. 16041148
Dufour, A., T. Hindré, D. Haras, and J.P. Le Pennec. (2007). The biology of lantibiotics from the lacticin 481 group is coming of age. FEMS Microbiol. Rev. 31: 134-167. 17096664
Okuda, K., S. Yanagihara, K. Shioya, Y. Harada, J. Nagao, Y. Aso, T. Zendo, J. Nakayama, and K. Sonomoto. (2008). Binding specificity of the lantibiotic-binding immunity protein NukH. Appl. Environ. Microbiol. 74: 7613-7619. 18978082
Okuda, K., Y. Aso, J. Nagao, K. Shioya, Y. Kanemasa, J. Nakayama, and K. Sonomoto. (2005). Characterization of functional domains of lantibiotic-binding immunity protein, NukH, from Staphylococcus warneri ISK-1. FEMS Microbiol. Lett. 250: 19-25. 16009508
Okuda, K., Y. Aso, J. Nakayama, and K. Sonomoto. (2008). Cooperative transport between NukFEG and NukH in immunity against the lantibiotic nukacin ISK-1 produced by Staphylococcus warneri ISK-1. J. Bacteriol. 190: 356-362. 17951378