Regulation of transcription by unnatural amino acids.
Small-molecule regulation of gene expression is intrinsic to cellular function and indispensable to the construction of new biological sensing, control and expression systems. However, there are currently only a handful of strategies for engineering such regulatory components and fewer still that can give rise to an arbitrarily large set of inducible systems whose members respond to different small molecules, display uniformity and modularity in their mechanisms of regulation, and combine to actuate universal logics. Here we present an approach for small-molecule regulation of transcription based on the combination of cis-regulatory leader-peptide elements with genetically encoded unnatural amino acids (amino acids that have been artificially added to the genetic code). In our system, any genetically encoded unnatural amino acid (UAA) can be used as a small-molecule attenuator or activator of gene transcription, and the logics intrinsic to the network defined by expanded genetic codes can be actuated.
Department of Bioengineering, University of California at Berkeley, Berkeley, California, USA. ccliu@berkeley.edu
Chang C
CC
Liu
Lei
L
Qi
Charles
C
Yanofsky
Adam P
AP
Arkin
D000596:Amino Acids / Q000378:metabolism*; D003062:Codon; D004926:Escherichia coli / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D008957:Models, Genetic; D050436:Regulatory Elements, Transcriptional; D013050:Spectrometry, Fluorescence; D014158:Transcription, Genetic
D000596:Amino Acids; D003062:Codon
Mol Syst Biol. 2007;3:133
17700541
Proc Natl Acad Sci U S A. 2004 May 18;101(20):7566-71
15138302
Microbiol Rev. 1996 Jun;60(2):366-85
8801438
Nature. 2004 Sep 23;431(7007):471-6
15386015
Angew Chem Int Ed Engl. 2010 Apr 19;49(18):3211-4
20340150
Nature. 2010 Mar 18;464(7287):441-4
20154731
J Am Chem Soc. 2010 Feb 24;132(7):2142-4
20121121
Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6234-9
20332210
Nature. 2009 Aug 13;460(7257):894-898
19633652
Nat Biotechnol. 2009 Dec;27(12):1139-50
20010597
J Am Chem Soc. 2002 Aug 7;124(31):9026-7
12148987
Brief Funct Genomic Proteomic. 2009 Nov;8(6):482-92
19651704
Nat Biotechnol. 2004 Jul;22(7):841-7
15208640
Science. 2008 Oct 17;322(5900):456-60
18927397
Nat Biotechnol. 2006 Jan;24(1):79-88
16369541
J Mol Biol. 2010 Jan 15;395(2):361-74
19852970
Curr Opin Microbiol. 2008 Dec;11(6):567-73
18983935
J Am Chem Soc. 2008 Dec 3;130(48):16310-5
18998646
J Biol Chem. 1989 Jul 25;264(21):12284-8
2663855
Annu Rev Microbiol. 2004;58:453-88
15487945
Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15898-903
20713708
J Mol Biol. 1990 Nov 5;216(1):25-37
2231731
Annu Rev Biochem. 2009;78:305-34
19298181
Mol Cell Biol. 2000 Dec;20(23):8635-42
11073965
Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):56-61
12518054
Annu Rev Genet. 1982;16:113-34
6186194
Science. 2002 Sep 13;297(5588):1864-7
12228716
ACS Chem Biol. 2008 Jan 18;3(1):64-76
18205292
Science. 2009 Dec 4;326(5958):1412-5
19933110
Annu Rev Biochem. 2010;79:413-44
20307192