title: Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.
abstract: Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.
authors.affiliation: Free Floater (Junior) Research Group Applied Synthetic Biology, Institute for Microbiology and Genetics, Georg-August University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen, Germany. hneumann@gwdg.de
authors.forename: Heinz
authors.initials: H
authors.lastname: Neumann
authors.forename: Petra
authors.initials: P
authors.lastname: Neumann-Staubitz
mesh_terms: D001419:Bacteria / Q000235:genetics* / Q000378:metabolism*; D001709:Biotechnology; D055808:Drug Discovery; D004345:Drug Industry; D005818:Genetic Engineering; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations
references.citation: Structure. 2006 Apr;14(4):737-48
references.pmid: 16564177
references.citation: Proc Natl Acad Sci U S A. 1979 Jan;76(1):106-10
references.pmid: 85300
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9774-8
references.pmid: 12888623
references.citation: Appl Environ Microbiol. 2002 Jul;68(7):3287-92
references.pmid: 12089005
references.citation: Mol Microbiol. 2003 Sep;49(6):1627-37
references.pmid: 12950926
references.citation: Anal Chem. 2003 Mar 15;75(6):1508-13
references.pmid: 12659216
references.citation: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15155-60
references.pmid: 11724950
references.citation: Chem Biol. 1999 Apr;6(4):R91-R105
references.pmid: 10099128
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20404-9
references.pmid: 19073939
references.citation: Nat Chem Biol. 2007 May;3(5):274-7
references.pmid: 17438551
references.citation: Nat Biotechnol. 2000 May;18(5):533-7
references.pmid: 10802621
references.citation: Appl Environ Microbiol. 2008 May;74(10):3229-41
references.pmid: 18344344
references.citation: Lancet Oncol. 2003 Sep;4(9):548-56
references.pmid: 12965276
references.citation: Nucleic Acids Res. 2003 Apr 1;31(7):1853-8
references.pmid: 12655001
references.citation: FEBS J. 2005 Jan;272(2):524-37
references.pmid: 15654890
references.citation: Nat Chem Biol. 2008 Apr;4(4):232-4
references.pmid: 18278036
references.citation: Curr Opin Microbiol. 2007 Jun;10(3):238-45
references.pmid: 17553731
references.citation: Trends Cell Biol. 2009 Nov;19(11):575-86
references.pmid: 19818623
references.citation: Science. 1998 Oct 9;282(5387):296-8
references.pmid: 9765156
references.citation: Curr Med Chem. 2005;12(6):717-39
references.pmid: 15790308
references.citation: Biotechnol Bioeng. 2006 Nov 5;95(4):684-91
references.pmid: 16878333
references.citation: Mol Syst Biol. 2007;3:158
references.pmid: 18091727
references.citation: Metab Eng. 2007 Jan;9(1):30-8
references.pmid: 17002894
references.citation: J Biol Chem. 2003 Oct 24;278(43):42020-6
references.pmid: 12923197
references.citation: Nat Biotechnol. 2006 Nov;24(11):1436-40
references.pmid: 17072302
references.citation: Science. 2008 Feb 29;319(5867):1215-20
references.pmid: 18218864
references.citation: Mol Syst Biol. 2007;3:133
references.pmid: 17700541
references.citation: Metab Eng. 2008 May-Jul;10(3-4):201-6
references.pmid: 18485776
references.citation: Nature. 2005 Nov 24;438(7067):441-2
references.pmid: 16306980
references.citation: Yeast. 2000 Jan 15;16(1):11-22
references.pmid: 10620771
references.citation: Int Rev Cytol. 2000;192:255-80
references.pmid: 10553282
references.citation: Nucleic Acids Res. 2004 Mar 05;32(4):1610-4
references.pmid: 15004248
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8414-9
references.pmid: 15159530
references.citation: J Antibiot (Tokyo). 2006 Aug;59(8):464-70
references.pmid: 17080682
references.citation: Nat Rev Microbiol. 2008 Sep;6(9):681-91
references.pmid: 18679172
references.citation: Cancer Gene Ther. 2003 Oct;10(10):737-44
references.pmid: 14502226
references.citation: Cell. 2010 Jan 8;140(1):33-47
references.pmid: 20085704
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11566-70
references.pmid: 15292507
references.citation: Trends Biotechnol. 2006 Feb;24(2):53-5
references.pmid: 16406119
references.citation: Science. 2009 Aug 14;325(5942):834-40
references.pmid: 19608861
references.citation: Curr Opin Biotechnol. 2008 Oct;19(5):468-74
references.pmid: 18725289
references.citation: Curr Opin Struct Biol. 2004 Aug;14(4):495-504
references.pmid: 15313245
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12678-83
references.pmid: 16123130
references.citation: Bioorg Med Chem Lett. 2004 Dec 6;14(23):5743-5
references.pmid: 15501033
references.citation: Nature. 2005 Jun 16;435(7044):983-7
references.pmid: 15959519
references.citation: Phytochemistry. 2001 Sep;58(1):1-7
references.pmid: 11524108
references.citation: Nature. 2004 Apr 22;428(6985):868-71
references.pmid: 15064770
references.citation: Protein Sci. 2007 Aug;16(8):1535-42
references.pmid: 17600141
references.citation: Nature. 2003 May 8;423(6936):185-90
references.pmid: 12736688
references.citation: Mol Cell. 2009 Oct 9;36(1):153-63
references.pmid: 19818718
references.citation: J Nat Prod. 1989 Sep-Oct;52(5):1183-5
references.pmid: 2607353
references.citation: Biochemistry. 2006 Jan 31;45(4):1321-30
references.pmid: 16430229
references.citation: J Am Chem Soc. 2009 Oct 14;131(40):14194-5
references.pmid: 19772323
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9846-51
references.pmid: 12097642
references.citation: Chem Biol. 2007 Mar;14(3):303-12
references.pmid: 17379145
references.citation: Gene Ther. 2001 Aug;8(15):1197-201
references.pmid: 11509951
references.citation: ACS Chem Biol. 2008 Dec 19;3(12):757-64
references.pmid: 19053244
references.citation: Cancer Res. 2010 Jan 1;70(1):18-23
references.pmid: 20028866
references.citation: ACS Chem Biol. 2009 Apr 17;4(4):261-7
references.pmid: 19271725
references.citation: Nature. 2006 Apr 20;440(7087):1078-82
references.pmid: 16495946
references.citation: Science. 2009 Sep 25;325(5948):1693-6
references.pmid: 19696314
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D26-31
references.pmid: 18940867
references.citation: Science. 2003 Aug 15;301(5635):964-7
references.pmid: 12920298
references.citation: Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):934-9
references.pmid: 8570663
references.citation: Nat Biotechnol. 2007 Jul;25(7):770-7
references.pmid: 17592474
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11124-9
references.pmid: 16844787
references.citation: Curr Med Chem. 2006;13(19):2221-32
references.pmid: 16918350
references.citation: Science. 2001 Apr 20;292(5516):498-500
references.pmid: 11313494
references.citation: Chem Rev. 2007 Sep;107(9):3715-43
references.pmid: 17715981
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13638-43
references.pmid: 10570125
references.citation: Protein Sci. 2007 Oct;16(10):2093-107
references.pmid: 17893358
references.citation: Nature. 1997 Aug 28;388(6645):882-7
references.pmid: 9278050
references.citation: Pharmacotherapy. 1997 Sep-Oct;17(5 Pt 2):110S-125S
references.pmid: 9322878
references.citation: Bioorg Med Chem. 2001 Sep;9(9):2237-42
references.pmid: 11553461
references.citation: Nat Methods. 2007 Mar;4(3):239-44
references.pmid: 17322890
references.citation: Mol Syst Biol. 2009;5:309
references.pmid: 19756048
references.citation: Mol Cell Proteomics. 2009 Feb;8(2):215-25
references.pmid: 18723842
references.citation: Planta Med. 1999 Feb;65(1):64-7
references.pmid: 10083848
references.citation: Mol Cell. 2006 Aug;23(4):607-18
references.pmid: 16916647
references.citation: Science. 2001 Mar 2;291(5509):1790-2
references.pmid: 11230695
references.citation: Fortschr Chem Org Naturst. 2002;84:53-225
references.pmid: 12132389
references.citation: Nat Biotechnol. 2009 Aug;27(8):753-9
references.pmid: 19648908
references.citation: J Am Chem Soc. 2009 Jul 1;131(25):8720-1
references.pmid: 19514718
references.citation: Science. 2007 Aug 3;317(5838):632-8
references.pmid: 17600181
references.citation: J Drug Target. 2003;11(8-10):471-9
references.pmid: 15203915
references.citation: Cancer Res. 1998 Mar 15;58(6):1111-5
references.pmid: 9515790
references.citation: Nat Biotechnol. 2005 Sep;23(9):1171-6
references.pmid: 16116420
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20683-8
references.pmid: 19075227
references.citation: J Am Chem Soc. 2003 Feb 19;125(7):1702-3
references.pmid: 12580587
references.citation: J Biol Chem. 2003 Jan 10;278(2):896-907
references.pmid: 12417595
references.citation: Curr Opin Chem Biol. 2009 Apr;13(2):135-43
references.pmid: 19217343
references.citation: Nature. 2010 Mar 18;464(7287):441-4
references.pmid: 20154731
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15591-6
references.pmid: 15498867
references.citation: Protein Sci. 2002 Nov;11(11):2655-75
references.pmid: 12381848
references.citation: J Am Chem Soc. 2005 Sep 7;127(35):12254-62
references.pmid: 16131203
references.citation: J Mol Biol. 2006 Jan 27;355(4):619-27
references.pmid: 16330045
references.citation: ACS Chem Biol. 2010 Jan 15;5(1):139-48
references.pmid: 20050612
references.citation: Curr Opin Biotechnol. 2006 Oct;17(5):548-57
references.pmid: 16978856
references.citation: J Biol Chem. 2003 May 23;278(21):19127-33
references.pmid: 12649277
references.citation: Mol Cell Biol. 1995 Nov;15(11):6188-95
references.pmid: 7565771
references.citation: Nature. 2009 Aug 13;460(7257):894-898
references.pmid: 19633652
references.citation: Nat Rev Mol Cell Biol. 2006 Oct;7(10):775-82
references.pmid: 16926858
references.citation: Nat Methods. 2009 May;6(5):343-5
references.pmid: 19363495
references.citation: Angew Chem Int Ed Engl. 2005 Apr 29;44(18):2760-2763
references.pmid: 15830403
references.citation: Nature. 2006 Apr 13;440(7086):940-3
references.pmid: 16612385
references.citation: Nat Biotechnol. 2003 Jul;21(7):796-802
references.pmid: 12778056
references.citation: Curr Opin Biotechnol. 2009 Aug;20(4):479-85
references.pmid: 19758796
references.citation: Curr Opin Microbiol. 2010 Apr;13(2):240-5
references.pmid: 20149718
references.citation: Nat Biotechnol. 2009 Dec;27(12):1139-50
references.pmid: 20010597
references.citation: Biotechnol Bioeng. 2006 Feb 5;93(2):212-24
references.pmid: 16161138
references.citation: Nature. 2008 May 8;453(7192):190-5
references.pmid: 18354394
references.citation: Appl Microbiol Biotechnol. 2001 Oct;57(1-2):13-9
references.pmid: 11693909