title: AS-48 bacteriocin: close to perfection.
abstract: Bacteriocin AS-48 is an intriguing molecule because of its unique structural characteristics, genetic regulation, broad activity spectrum, and potential biotechnological applications. It was the first reported circular bacteriocin and has been undoubtedly the best characterized for the last 25 years. Thus, AS-48 is the prototype of circular bacteriocins (class IV), for which the structure and genetic regulation have been elucidated. This review discusses the state-of-the-art in genetic engineering with regard to this circular protein, with the use of site-directed mutagenesis and circular permutation. Mutagenesis studies have been used to unravel the role of (a) different residues in the biological activity, underlining the relevance of several residues involved in membrane interaction and the low correlation between stability and activity and (b) three amino acids involved in maturation, providing information on the specificity of the leader peptidase and the circularization process itself. To investigate the role of circularity in the stability and biological properties of the enterocin AS-48, two different ways of linearization have been attempted: in vitro by limited proteolysis experiments and in vivo by circular permutation in the structural gene as-48A. The results summarized here show the significance of circularization on the secondary structure, potency and, especially, the stability of AS-48 and point as well to a putative role of the leader peptide as a protecting moiety in the pre-proprotein. Taken all together, the data available on circular bacteriocins support the idea that AS-48 has been engineered by nature to make a remarkably active and stable protein with a broad spectrum of activity.
authors: Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Armilla (Granada), Spain.
authors: Marina
authors: M
authors: Sánchez-Hidalgo
authors: Manuel
authors: M
authors: Montalbán-López
authors: Rubén
authors: R
authors: Cebrián
authors: Eva
authors: E
authors: Valdivia
authors: Manuel
authors: M
authors: Martínez-Bueno
authors: Mercedes
authors: M
authors: Maqueda
references: Annu Rev Microbiol. 2007;61:477-501
references: 17506681
references: Biochemistry. 2002 Jul 30;41(30):9508-15
references: 12135373
references: Appl Environ Microbiol. 1997 Feb;63(2):394-402
references: 9023920
references: Biochimie. 2011 Mar;93(3):549-55
references: 21130135
references: Annu Rev Microbiol. 2002;56:117-37
references: 12142491
references: J Am Chem Soc. 2003 Apr 23;125(16):4726-7
references: 12696888
references: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D192-4
references: 16381843
references: J Biol Chem. 2009 Oct 16;284(42):28674-81
references: 19692336
references: Biochim Biophys Acta. 2002 Jul 29;1598(1-2):98-107
references: 12147349
references: J Bacteriol. 2008 Jan;190(1):240-50
references: 17981958
references: Biopolymers. 2010;94(5):573-83
references: 20564019
references: Int J Food Microbiol. 2010 Jun 30;141(1-2):1-10
references: 20399522
references: Protein Pept Lett. 2010 Jun;17(6):708-14
references: 19958277
references: Science. 2006 Sep 15;313(5793):1636-7
references: 16973881
references: Curr Protein Pept Sci. 2004 Oct;5(5):393-8
references: 15544534
references: FEMS Microbiol Rev. 2008 Jan;32(1):2-22
references: 18034824
references: Syst Appl Microbiol. 2005 Jul;28(5):383-97
references: 16094865
references: FEBS Lett. 2004 Nov 19;577(3):399-402
references: 15556617
references: Appl Environ Microbiol. 2003 Jul;69(7):3777-83
references: 12839744
references: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W382-8
references: 15980494
references: Appl Environ Microbiol. 2011 Jan;77(2):604-11
references: 21097596
references: J Biol Chem. 2001 May 11;276(19):16548-54
references: 11278952
references: Mol Microbiol. 1998 Jan;27(2):347-58
references: 9484890
references: Appl Environ Microbiol. 2010 Nov;76(21):7268-76
references: 20833793
references: FEBS Lett. 2008 Sep 22;582(21-22):3237-42
references: 18760277
references: Trends Biochem Sci. 2000 Sep;25(9):429-34
references: 10973056
references: Curr Protein Pept Sci. 2004 Oct;5(5):399-416
references: 15544535
references: Appl Environ Microbiol. 2008 Aug;74(15):4756-63
references: 18552180
references: J Pept Sci. 2005 Jan;11(1):29-36
references: 15635724
references: Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12298-303
references: 12198183
references: Appl Environ Microbiol. 2004 Aug;70(8):4672-80
references: 15294801
references: Appl Environ Microbiol. 2011 Jan;77(1):369-73
references: 21057028
references: Probiotics Antimicrob Proteins. 2010 Jun;2(2):77-89
references: 26781116
references: Appl Microbiol Biotechnol. 2004 Jun;64(6):806-15
references: 15048591
references: Appl Environ Microbiol. 2009 Mar;75(6):1552-8
references: 19139222
references: Appl Microbiol Biotechnol. 2003 Jan;60(5):523-33
references: 12536251
references: Biochemistry. 2000 May 30;39(21):6521-8
references: 10828968
references: Chem Rev. 2005 Mar;105(3):973-99
references: 15755082
references: Appl Environ Microbiol. 2003 Oct;69(10):5839-48
references: 14532033
references: Biophys J. 2007 Sep 15;93(6):1858-71
references: 17496025
references: Chem Biol. 2009 Dec 24;16(12):1290-8
references: 20064439
references: J Antimicrob Chemother. 2008 Jun;61(6):1256-65
references: 18385141
references: Lett Appl Microbiol. 2010 Apr;50(4):406-11
references: 20156306
references: Nat Chem Biol. 2010 Jan;6(1):9-18
references: 20016494
references: Curr Mol Pharmacol. 2010 Nov;3(3):153-63
references: 20858197
references: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13638-43
references: 10570125
references: Biochemistry. 2004 Mar 30;43(12):3385-95
references: 15035610
references: Microbiology (Reading). 2007 May;153(Pt 5):1619-1630
references: 17464077
references: J Mol Biol. 2001 Feb 9;306(1):121-32
references: 11178898
references: Phys Biol. 2009 Feb 04;6(1):013001
references: 19193974
references: J Mol Biol. 2006 Apr 14;357(5):1522-35
references: 16488428
references: Org Biomol Chem. 2010 Nov 21;8(22):5035-47
references: 20835453