Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.
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.
Neumann
Heinz
H
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
Neumann-Staubitz
Petra
P
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
D004364:Pharmaceutical Preparations
Structure. 2006 Apr;14(4):737-48
16564177
Proc Natl Acad Sci U S A. 1979 Jan;76(1):106-10
85300
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9774-8
12888623
Appl Environ Microbiol. 2002 Jul;68(7):3287-92
12089005
Mol Microbiol. 2003 Sep;49(6):1627-37
12950926
Anal Chem. 2003 Mar 15;75(6):1508-13
12659216
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15155-60
11724950
Chem Biol. 1999 Apr;6(4):R91-R105
10099128
Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20404-9
19073939
Nat Chem Biol. 2007 May;3(5):274-7
17438551
Nat Biotechnol. 2000 May;18(5):533-7
10802621
Appl Environ Microbiol. 2008 May;74(10):3229-41
18344344
Lancet Oncol. 2003 Sep;4(9):548-56
12965276
Nucleic Acids Res. 2003 Apr 1;31(7):1853-8
12655001
FEBS J. 2005 Jan;272(2):524-37
15654890
Nat Chem Biol. 2008 Apr;4(4):232-4
18278036
Curr Opin Microbiol. 2007 Jun;10(3):238-45
17553731
Trends Cell Biol. 2009 Nov;19(11):575-86
19818623
Science. 1998 Oct 9;282(5387):296-8
9765156
Curr Med Chem. 2005;12(6):717-39
15790308
Biotechnol Bioeng. 2006 Nov 5;95(4):684-91
16878333
Mol Syst Biol. 2007;3:158
18091727
Metab Eng. 2007 Jan;9(1):30-8
17002894
J Biol Chem. 2003 Oct 24;278(43):42020-6
12923197
Nat Biotechnol. 2006 Nov;24(11):1436-40
17072302
Science. 2008 Feb 29;319(5867):1215-20
18218864
Mol Syst Biol. 2007;3:133
17700541
Metab Eng. 2008 May-Jul;10(3-4):201-6
18485776
Nature. 2005 Nov 24;438(7067):441-2
16306980
Yeast. 2000 Jan 15;16(1):11-22
10620771
Int Rev Cytol. 2000;192:255-80
10553282
Nucleic Acids Res. 2004 Mar 05;32(4):1610-4
15004248
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8414-9
15159530
J Antibiot (Tokyo). 2006 Aug;59(8):464-70
17080682
Nat Rev Microbiol. 2008 Sep;6(9):681-91
18679172
Cancer Gene Ther. 2003 Oct;10(10):737-44
14502226
Cell. 2010 Jan 8;140(1):33-47
20085704
Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11566-70
15292507
Trends Biotechnol. 2006 Feb;24(2):53-5
16406119
Science. 2009 Aug 14;325(5942):834-40
19608861
Curr Opin Biotechnol. 2008 Oct;19(5):468-74
18725289
Curr Opin Struct Biol. 2004 Aug;14(4):495-504
15313245
Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12678-83
16123130
Bioorg Med Chem Lett. 2004 Dec 6;14(23):5743-5
15501033
Nature. 2005 Jun 16;435(7044):983-7
15959519
Phytochemistry. 2001 Sep;58(1):1-7
11524108
Nature. 2004 Apr 22;428(6985):868-71
15064770
Protein Sci. 2007 Aug;16(8):1535-42
17600141
Nature. 2003 May 8;423(6936):185-90
12736688
Mol Cell. 2009 Oct 9;36(1):153-63
19818718
J Nat Prod. 1989 Sep-Oct;52(5):1183-5
2607353
Biochemistry. 2006 Jan 31;45(4):1321-30
16430229
J Am Chem Soc. 2009 Oct 14;131(40):14194-5
19772323
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9846-51
12097642
Chem Biol. 2007 Mar;14(3):303-12
17379145
Gene Ther. 2001 Aug;8(15):1197-201
11509951
ACS Chem Biol. 2008 Dec 19;3(12):757-64
19053244
Cancer Res. 2010 Jan 1;70(1):18-23
20028866
ACS Chem Biol. 2009 Apr 17;4(4):261-7
19271725
Nature. 2006 Apr 20;440(7087):1078-82
16495946
Science. 2009 Sep 25;325(5948):1693-6
19696314
Nucleic Acids Res. 2009 Jan;37(Database issue):D26-31
18940867
Science. 2003 Aug 15;301(5635):964-7
12920298
Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):934-9
8570663
Nat Biotechnol. 2007 Jul;25(7):770-7
17592474
Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11124-9
16844787
Curr Med Chem. 2006;13(19):2221-32
16918350
Science. 2001 Apr 20;292(5516):498-500
11313494
Chem Rev. 2007 Sep;107(9):3715-43
17715981
Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13638-43
10570125
Protein Sci. 2007 Oct;16(10):2093-107
17893358
Nature. 1997 Aug 28;388(6645):882-7
9278050
Pharmacotherapy. 1997 Sep-Oct;17(5 Pt 2):110S-125S
9322878
Bioorg Med Chem. 2001 Sep;9(9):2237-42
11553461
Nat Methods. 2007 Mar;4(3):239-44
17322890
Mol Syst Biol. 2009;5:309
19756048
Mol Cell Proteomics. 2009 Feb;8(2):215-25
18723842
Planta Med. 1999 Feb;65(1):64-7
10083848
Mol Cell. 2006 Aug;23(4):607-18
16916647
Science. 2001 Mar 2;291(5509):1790-2
11230695
Fortschr Chem Org Naturst. 2002;84:53-225
12132389
Nat Biotechnol. 2009 Aug;27(8):753-9
19648908
J Am Chem Soc. 2009 Jul 1;131(25):8720-1
19514718
Science. 2007 Aug 3;317(5838):632-8
17600181
J Drug Target. 2003;11(8-10):471-9
15203915
Cancer Res. 1998 Mar 15;58(6):1111-5
9515790
Nat Biotechnol. 2005 Sep;23(9):1171-6
16116420
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20683-8
19075227
J Am Chem Soc. 2003 Feb 19;125(7):1702-3
12580587
J Biol Chem. 2003 Jan 10;278(2):896-907
12417595
Curr Opin Chem Biol. 2009 Apr;13(2):135-43
19217343
Nature. 2010 Mar 18;464(7287):441-4
20154731
Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15591-6
15498867
Protein Sci. 2002 Nov;11(11):2655-75
12381848
J Am Chem Soc. 2005 Sep 7;127(35):12254-62
16131203
J Mol Biol. 2006 Jan 27;355(4):619-27
16330045
ACS Chem Biol. 2010 Jan 15;5(1):139-48
20050612
Curr Opin Biotechnol. 2006 Oct;17(5):548-57
16978856
J Biol Chem. 2003 May 23;278(21):19127-33
12649277
Mol Cell Biol. 1995 Nov;15(11):6188-95
7565771
Nature. 2009 Aug 13;460(7257):894-898
19633652
Nat Rev Mol Cell Biol. 2006 Oct;7(10):775-82
16926858
Nat Methods. 2009 May;6(5):343-5
19363495
Angew Chem Int Ed Engl. 2005 Apr 29;44(18):2760-2763
15830403
Nature. 2006 Apr 13;440(7086):940-3
16612385
Nat Biotechnol. 2003 Jul;21(7):796-802
12778056
Curr Opin Biotechnol. 2009 Aug;20(4):479-85
19758796
Curr Opin Microbiol. 2010 Apr;13(2):240-5
20149718
Nat Biotechnol. 2009 Dec;27(12):1139-50
20010597
Biotechnol Bioeng. 2006 Feb 5;93(2):212-24
16161138
Nature. 2008 May 8;453(7192):190-5
18354394
Appl Microbiol Biotechnol. 2001 Oct;57(1-2):13-9
11693909