Plasmid addiction systems: perspectives and applications in biotechnology.
Biotechnical production processes often operate with plasmid-based expression systems in well-established prokaryotic and eukaryotic hosts such as Escherichia coli or Saccharomyces cerevisiae, respectively. Genetically engineered organisms produce important chemicals, biopolymers, biofuels and high-value proteins like insulin. In those bioprocesses plasmids in recombinant hosts have an essential impact on productivity. Plasmid-free cells lead to losses in the entire product recovery and decrease the profitability of the whole process. Use of antibiotics in industrial fermentations is not an applicable option to maintain plasmid stability. Especially in pharmaceutical or GMP-based fermentation processes, deployed antibiotics must be inactivated and removed. Several plasmid addiction systems (PAS) were described in the literature. However, not every system has reached a full applicable state. This review compares most known addiction systems and is focusing on biotechnical applications.
Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.
Jens
J
Kroll
Stefan
S
Klinter
Cornelia
C
Schneider
Isabella
I
Voss
Alexander
A
Steinbüchel
D001709:Biotechnology / Q000379:methods*; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D015870:Gene Expression; D042822:Genomic Instability; D050296:Microbial Viability; D010957:Plasmids; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism
J Mol Biol. 1993 Oct 5;233(3):414-28
8411153
J Bacteriol. 2000 May;182(9):2416-21
10762240
Biotechnol Prog. 2005 Mar-Apr;21(2):343-8
15801769
J Biol Chem. 2009 Oct 16;284(42):28746-53
19690171
J Biol Chem. 2006 Dec 8;281(49):37942-51
16982615
Arch Mikrobiol. 1968;62(2):129-43
4974905
J Biol Chem. 1993 Dec 25;268(36):27109-17
8262949
Mol Microbiol. 2002 Jul;45(2):333-49
12123448
FEBS Lett. 2008 Mar 5;582(5):710-4
18258191
Biochem Biophys Res Commun. 1976 Sep 7;72(1):355-62
985479
J Bacteriol. 2007 Jul;189(14):5041-8
17496075
J Bacteriol. 2005 Oct;187(19):6612-21
16166522
J Mol Biol. 1984 Apr 25;174(4):605-25
6327993
J Bacteriol. 2002 Nov;184(22):6100-8
12399478
Mol Microbiol. 1998 Aug;29(4):1065-76
9767574
Science. 1983 Feb 11;219(4585):632-7
6337396
Biochimie. 1999 Aug-Sep;81(8-9):931-8
10572308
J Bacteriol. 1992 Jul;174(13):4205-11
1624414
J Bacteriol. 2001 Mar;183(6):2041-5
11222603
Cell. 2008 Jan 11;132(1):55-66
18191220
Proc Natl Acad Sci U S A. 1972 Nov;69(11):3448-52
4343974
Genome Biol. 2003;4(12):R81
14659018
J Bacteriol. 1992 Dec;174(24):8119-32
1459960
Nucleic Acids Res. 1987 Jan 12;15(1):313-32
3029675
Nucleic Acids Res. 1998 May 1;26(9):2120-4
9547269
Annu Rev Biochem. 1968;37:79-108
4875725
EMBO J. 1993 Nov;12(11):4297-303
7693455
Biomol Eng. 1999 Dec 31;16(1-4):135-40
10796996
Ann N Y Acad Sci. 2007 Jun;1105:325-50
17395730
Biochem Biophys Res Commun. 2005 Feb 18;327(3):637-9
15649393
Gene. 1995 Aug 30;162(1):159-60
7557407
Biol Chem. 2002 Nov;383(11):1701-13
12530535
J Bacteriol. 2004 Oct;186(19):6400-8
15375120
J Biotechnol. 2004 Jul 1;111(1):17-30
15196766
Nat Biotechnol. 2006 Oct;24(10):1257-62
16964242
Infect Immun. 2000 Feb;68(2):896-905
10639460
Appl Microbiol Biotechnol. 2005 May;67(3):289-98
15635462
Proc Natl Acad Sci U S A. 1986 May;83(10):3116-20
3517851
J Bacteriol. 1993 Nov;175(21):6850-6
8226627
J Bacteriol. 1996 Apr;178(7):2086-93
8606188
Mol Microbiol. 2006 Oct;62(2):397-411
17020579
J Bacteriol. 2000 Apr;182(8):2218-29
10735865
Curr Opin Biotechnol. 2000 Jun;11(3):262-70
10851148
Bacteriol Rev. 1972 Dec;36(4):407-77
4568761
Bioessays. 2005 May;27(5):563-73
15832375
Mol Microbiol. 1992 Jun;6(12):1631-43
1495391
Proc Natl Acad Sci U S A. 1998 May 26;95(11):6442-7
9600985
J Bacteriol. 2001 Dec;183(24):7403-7
11717301
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1158-63
11818558
Mol Gen Genet. 1993 Feb;237(1-2):81-8
8455570
Metab Eng. 2009 May;11(3):168-77
19558962
J Bacteriol. 1998 Oct;180(20):5458-62
9765581
Nucleic Acids Res. 2006;34(20):5915-22
17065468
Lett Appl Microbiol. 2003;37(4):318-23
12969496
Appl Environ Microbiol. 1997 May;63(5):1917-24
9143123
J Bacteriol. 1995 Jun;177(12):3451-4
7768854
Antimicrob Agents Chemother. 2003 Apr;47(4):1301-7
12654662
EMBO J. 1994 Sep 1;13(17):3927-35
8076590
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3274-7
7724551
FEBS Lett. 2007 May 1;581(9):1727-34
17416361
Proc Natl Acad Sci U S A. 1968 Apr;59(4):1259-64
4870861
J Bacteriol. 1991 Sep;173(18):5732-9
1715862
Gene. 1994 Oct 11;148(1):71-4
7926841
Vaccine. 1997 Apr-May;15(6-7):700-8
9178472
Mol Microbiol. 2000 Aug;37(3):652-60
10931358
Infect Immun. 1997 Aug;65(8):3381-5
9234801
Appl Environ Microbiol. 1993 May;59(5):1361-6
8517732
Infect Immun. 2006 Jul;74(7):4383-6
16790817
J Bacteriol. 2006 May;188(9):3420-3
16621839
Biochem Biophys Res Commun. 1996 Mar 18;220(2):280-4
8645296
Biol Reprod. 1995 Aug;53(2):462-71
7492701
Mol Microbiol. 2003 Jun;48(5):1389-400
12787364
Appl Environ Microbiol. 2001 Jun;67(6):2649-56
11375176
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14328-33
11717402
Biotechnol Bioeng. 1994 Oct;44(8):912-21
18618909
Nucleic Acids Res. 2004 Jun 09;32(10):3136-47
15190131
Nat Rev Microbiol. 2005 May;3(5):371-82
15864262
Microbiology (Reading). 2006 Nov;152(Pt 11):3425-3435
17074911
Mol Microbiol. 1996 Apr;20(1):53-63
8861204
Biotechnol Bioeng. 1997 May 20;54(4):391-9
18634106
Microbiology (Reading). 2003 Dec;149(Pt 12):3595-3601
14663091
Nat Rev Microbiol. 2003 Oct;1(1):35-44
15040178
Nucleic Acids Res. 2003 Mar 15;31(6):1633-9
12626704
Infect Immun. 1996 Oct;64(10):4172-81
8926085
J Biol Chem. 1988 Oct 25;263(30):15699-704
2844820
Annu Rev Genet. 1997;31:1-31
9442888
J Bacteriol. 2005 Sep;187(17):6094-105
16109951
J Biol Chem. 1984 Dec 10;259(23):14824-8
6094577
Mol Cell Biol. 1990 Sep;10(9):4538-44
2201894
J Bacteriol. 1998 Sep;180(17):4693-703
9721313
Appl Microbiol Biotechnol. 1992 Oct;38(1):91-3
1369014
Arch Mikrobiol. 1964 Apr 2;48:95-108
14249035
Crit Rev Biotechnol. 2006 Jul-Sep;26(3):145-64
16923532
J Mol Biol. 1994 Mar 11;236(5):1289-98
8126720
J Antimicrob Chemother. 2005 Jun;55(6):983-8
15872045
EMBO J. 1986 Aug;5(8):2023-9
3019679
Trends Biotechnol. 2003 May;21(5):187-90
12727376
Infect Immun. 2005 Dec;73(12):8345-52
16299332
ISME J. 2008 Jun;2(6):615-31
18309357
Acta Biochim Pol. 2001;48(4):1003-23
11995964
J Biol Chem. 1986 Dec 25;261(36):17113-9
3023382
Nucleic Acids Res. 1997 Jun 1;25(11):2114-20
9153310
Nucleic Acids Res. 1997 Jul 15;25(14):2702-15
9207015
J Biol Chem. 2003 Aug 22;278(34):32300-6
12810711
Mol Microbiol. 2006 Jan;59(2):590-601
16390452
Annu Rev Biochem. 2006;75:567-605
16756503
J Bacteriol. 2003 Mar;185(6):1803-7
12618443
Plasmid. 1994 Sep;32(2):168-81
7531349
Appl Environ Microbiol. 1991 Jan;57(1):85-92
2036024
Mol Microbiol. 1993 Sep;9(5):1089-95
7523831
FEMS Microbiol Lett. 2000 Jun 1;187(1):41-5
10828398
Infect Immun. 1998 Jan;66(1):224-31
9423862
Antimicrob Agents Chemother. 1996 Aug;40(8):1801-5
8843284
J Bacteriol. 1990 Nov;172(11):6194-203
2172207
J Bacteriol. 2009 Feb;191(4):1258-67
19060153
Annu Rev Microbiol. 1993;47:139-66
8257096
Mol Microbiol. 2003 Nov;50(4):1199-213
14622409
Infect Immun. 2005 Apr;73(4):2005-11
15784541
J Biol Chem. 1999 Jun 11;274(24):16813-8
10358024
Infect Immun. 1995 Dec;63(12):4557-63
7591105
Antimicrob Agents Chemother. 2004 Oct;48(10):3817-22
15388440
J Biol Chem. 2007 Jul 6;282(27):19606-18
17488720
Plasmid. 2001 Nov;46(3):210-22
11735370
J Bacteriol. 1989 May;171(5):2353-60
2651399
Mol Microbiol. 1992 Jul;6(14):1969-79
1508044
Mol Gen Genet. 1989 Oct;219(1-2):26-32
2615761
EMBO J. 1985 Apr;4(4):1059-66
2990907
Metab Eng. 2006 Jan;8(1):66-78
16266816
J Mol Biol. 1992 Aug 5;226(3):637-49
1380562
Plasmid. 2007 Sep;58(2):115-26
17395262
Ann N Y Acad Sci. 2007 Jun;1105:67-97
17395725
J Bacteriol. 2005 Oct;187(19):6641-50
16166525
PLoS One. 2009 Aug 26;4(8):e6785
19707553
Mol Microbiol. 2007 Mar;63(6):1588-605
17367382
Bioinformatics. 2006 Nov 1;22(21):2581-4
16895922
Antonie Van Leeuwenhoek. 1995;67(3):261-79
7778895
Appl Environ Microbiol. 1993 Nov;59(11):3713-7
8285679
Mol Microbiol. 1999 Jun;32(5):1090-102
10361310
Curr Genet. 1998 Jul;34(1):60-6
9683676
Appl Microbiol Biotechnol. 2002 Jul;59(2-3):143-52
12111139
J Cell Sci. 2005 Oct 1;118(Pt 19):4327-32
16179604
Biochem Biophys Res Commun. 2010 Jan 1;391(1):209-13
19909729
Int Microbiol. 2005 Sep;8(3):213-22
16200500
BMC Biotechnol. 2008 Jan 14;8:2
18194555
J Bacteriol. 1983 Aug;155(2):768-75
6348026
Mol Gen Genet. 1987 Nov;210(1):101-10
3323833
Gene. 1995 May 19;157(1-2):25-9
7607501
Annu Rev Genet. 1989;23:37-69
2694936
Trends Biotechnol. 2002 Jun;20(6):243-8
12007492
Appl Microbiol Biotechnol. 2007 Oct;76(5):957-67
17657486
Biotechnol J. 2006 Jun;1(6):675-81
16892316
Appl Environ Microbiol. 1996 May;62(5):1805-7
16535323
Mol Microbiol. 2002 Jul;45(2):501-10
12123459
Microbiology (Reading). 2005 Feb;151(Pt 2):421-431
15699191
Appl Environ Microbiol. 1988 Oct;54(10):2472-7
3060017
Mol Microbiol. 1995 Jul;17(2):205-10
7494469
J Bacteriol. 2007 Sep;189(17):6089-92
17616596
J Mol Biol. 2007 Sep 28;372(4):894-905
17706670
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):728-33
10639147
Ann N Y Acad Sci. 2007 Jun;1105:405-17
17416926
J Bacteriol. 1988 Apr;170(4):1461-6
2832364
Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1059-63
9037005
J Bacteriol. 1991 Feb;173(4):1367-75
1995588
J Mol Biol. 2003 Sep 26;332(4):809-19
12972253
Nucleic Acids Res. 2005 Feb 17;33(3):966-76
15718296
BMC Genomics. 2006 Oct 13;7:259
17038198
J Bacteriol. 2004 Jun;186(11):3663-9
15150257
PLoS Pathog. 2009 Dec;5(12):e1000706
20041169
Yeast. 2005 Mar;22(4):249-70
15704221
Antimicrob Agents Chemother. 1998 Dec;42(12):3282-4
9835528
Nat Rev Microbiol. 2005 Feb;3(2):119-28
15685223
J Clin Microbiol. 1985 Aug;22(2):212-5
4031036
J Biol Chem. 2004 Feb 27;279(9):8252-61
14672926
J Biotechnol. 2005 Jan 26;115(2):113-28
15607230
Biochim Biophys Acta. 1976 Feb 13;422(2):407-18
2311
Mol Microbiol. 2007 May;64(3):738-54
17462020
J Biol Chem. 1999 Jan 29;274(5):2652-7
9915794
EMBO J. 1988 Jun;7(6):1889-95
2844527
Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11095-9
7479944
J Bacteriol. 2000 Feb;182(3):561-72
10633087
Appl Microbiol Biotechnol. 2007 Nov;77(2):257-67
17876577
JAMA. 2001 Jun 6;285(21):2763-73
11386933
Gene. 1995 May 19;157(1-2):73-9
7607530
Annu Rev Genet. 1991;25:585-627
1812816
EMBO J. 2003 Jan 15;22(2):246-51
12514130
Mol Microbiol. 2003 Mar;47(5):1419-32
12603745
Cell. 1984 Apr;36(4):1097-103
6323019
Gene. 1994 May 27;143(1):1-12
8200522
Appl Environ Microbiol. 1995 Mar;61(3):985-91
7793926
J Mol Biol. 1992 Jan 5;223(1):41-54
1370544
J Bacteriol. 2007 Sep;189(17):6101-8
17513477
Mol Microbiol. 2002 May;44(4):971-9
12010492
J Bacteriol. 1986 May;166(2):399-403
3516974
Curr Opin Microbiol. 2006 Jun;9(3):268-74
16617034
J Bacteriol. 1996 Mar;178(5):1420-9
8631720
Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):405-9
1703297
Curr Protoc Protein Sci. 2001 May;Chapter 5:Unit5.6
18429187
Infect Immun. 1999 Dec;67(12):6424-33
10569759
Appl Environ Microbiol. 2000 Dec;66(12):5524-6
11097943
J Bacteriol. 2007 Jan;189(2):491-500
17085558
Mol Plant Microbe Interact. 2006 Jul;19(7):811-22
16838793
J Environ Monit. 1999 Dec;1(6):108N-110N
11529177
Plasmid. 2006 Jul;56(1):68-73
16442621
Appl Environ Microbiol. 1995 Aug;61(8):2990-4
7487030
J Bacteriol. 2008 Jul;190(13):4603-9
18441063
Infect Immun. 1992 Nov;60(11):4586-92
1398971
Appl Environ Microbiol. 1991 May;57(5):1504-8
16348490
Science. 2007 Oct 26;318(5850):652-5
17962566
Genome Biol. 2007;8(8):R155
17678530
J Bacteriol. 1994 Jul;176(13):4081-91
8021189
J Bacteriol. 2001 Mar;183(6):2046-50
11222604
Annu Rev Microbiol. 1999;53:43-70
10547685
J Biol Chem. 1996 Aug 2;271(31):18705-10
8702525
Nucleic Acids Res. 2001 Mar 1;29(5):E26
11222777
FEMS Immunol Med Microbiol. 1996 Mar;13(3):257-60
8861040
Genetics. 1991 May;128(1):23-7
1829427
FEMS Microbiol Lett. 2007 Mar;268(1):112-9
17263853
J Mol Microbiol Biotechnol. 1999 Nov;1(2):295-302
10943559
Mol Plant Microbe Interact. 2001 Jul;14(7):887-94
11437262
Proc Natl Acad Sci U S A. 1982 Oct;79(20):6313-7
6183660
Appl Environ Microbiol. 1995 Feb;61(2):481-6
7574584
J Bacteriol. 1985 Sep;163(3):841-9
3897195
Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6059-63
8650219
Infect Immun. 1997 May;65(5):1926-30
9125581
Microbiology (Reading). 1999 Mar;145 ( Pt 3):515-516
10217483
J Bacteriol. 2007 Feb;189(4):1266-78
17071753
Microbiology (Reading). 2006 Aug;152(Pt 8):2365-2379
16849801
Gene. 1993 Dec 22;136(1-2):1-12
8293991
Antimicrob Agents Chemother. 2005 Aug;49(8):3203-7
16048926
J Bacteriol. 1998 Dec;180(23):6342-51
9829946
Mol Microbiol. 2001 Jul;41(1):73-82
11454201
J Mol Biol. 1984 Apr 25;174(4):627-46
6233425
J Mol Microbiol Biotechnol. 2004;7(4):197-203
15383717
FEMS Microbiol Rev. 2002 Nov;26(4):339-53
12413664
Biotechnology (N Y). 1996 Feb;14(2):189-91
9636322
Trends Biochem Sci. 2005 Dec;30(12):672-9
16257530
Adv Biochem Eng Biotechnol. 2004;86:47-82
15088763
J Biol Chem. 1955 Apr;213(2):757-67
14367336
Nat Biotechnol. 2001 Apr;19(4):360-4
11283595
Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1661-6
12571357
J Bacteriol. 2008 Mar;190(6):2039-49
18192396
Mol Microbiol. 1992 Jul;6(14):1981-94
1508045
Curr Biol. 2000 Dec 14-28;10(24):R888-90
11137022
FEMS Microbiol Lett. 1996 Aug 15;142(1):1-10
8759784
Proc Natl Acad Sci U S A. 1983 Aug;80(15):4784-8
6308648
Mol Gen Genet. 1993 Dec;241(5-6):579-85
8264532