Thiamine biosynthesis can be used to dissect metabolic integration.
The emergence of systems biology has re-emphasized the advantages of understanding biological processes with a global perspective. One biological process amenable to global approaches is microbial metabolism. This review describes a model system that contributes to the goals of systems biology by experimentally defining metabolic integration found in a bacterial cell and thus providing data needed for implementation and interpretation of systems approaches. We have taken a largely unbiased in vivo approach centered on thiamine biosynthesis to identify new metabolic components and connections, and to explore uncharacterized paradigms of the integration between them. This article summarizes recent results from this approach that include the identification of the function of unknown genes, connections between cofactors biosynthesis and thiamine biosynthesis, and how metabolites from one biosynthetic pathway can be used in thiamine biosynthesis.
Koenigsknecht
Mark J
MJ
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Downs
Diana M
DM
D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D005798:Genes, Bacterial; D005809:Genes, Regulator; D008954:Models, Biological; D012268:Ribose-Phosphate Pyrophosphokinase / Q000378:metabolism; D019779:Salmonella enterica / Q000235:genetics / Q000378:metabolism*; D049490:Systems Biology / Q000379:methods; D013831:Thiamine / Q000096:biosynthesis* / Q000378:metabolism
D012268:Ribose-Phosphate Pyrophosphokinase; D013831:Thiamine
Biotechnol Bioeng. 2003 Dec 30;84(7):887-99
14708128
Curr Opin Biotechnol. 2006 Oct;17(5):448-56
16978855
Trends Biotechnol. 2008 Sep;26(9):490-7
18675480
Microbiology (Reading). 2010 Mar;156(Pt 3):950-959
19959576
FEMS Microbiol Rev. 2009 Jan;33(1):191-205
19054113
J Bacteriol. 2008 Feb;190(3):815-22
17557816
J Bacteriol. 2000 Jan;182(1):236-40
10613889
Acta Crystallogr D Biol Crystallogr. 2003 Sep;59(Pt 9):1676-8
12925811
Metab Eng. 2006 Jan;8(1):1-13
16199194
J Bacteriol. 2003 Jan;185(1):98-106
12486045
Nat Rev Microbiol. 2009 Feb;7(2):129-43
19116616
J Mol Biol. 1995 Oct 6;252(5):536-49
7563072
Annu Rev Microbiol. 2006;60:533-59
16771650
EMBO J. 2003 Jun 2;22(11):2614-22
12773378
Can J Microbiol. 1999 Jul;45(7):565-72
10497788
Int J Biol Macromol. 2005 Oct 30;37(1-2):61-8
16198412
Nat Chem Biol. 2007 May;3(5):278-86
17401378
BMC Struct Biol. 2007 May 16;7:30
17506874
Nat Chem Biol. 2008 Dec;4(12):758-65
18953358
Nat Biotechnol. 2005 May;23(5):612-6
15821729
Biochemistry. 2008 Sep 2;47(35):9054-6
18686975
J Bacteriol. 1996 Oct;178(19):5676-82
8824612
J Bacteriol. 2004 Feb;186(3):803-10
14729707
Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8030-5
11416172
J Bacteriol. 1998 Dec;180(24):6519-28
9851994
Protein Sci. 1999 Nov;8(11):2428-37
10595546
Nat Rev Microbiol. 2009 Mar;7(3):196-205
19219053
J Biol Chem. 1968 Nov 10;243(21):5605-9
5699054
J Biol Chem. 2004 Apr 23;279(17):17054-62
14757766
J Bacteriol. 2006 Oct;188(19):6786-92
16980480
J Membr Biol. 1993 Dec;136(3):281-8
8114078
Nat Prod Rep. 2003 Apr;20(2):184-201
12735696
Nat Biotechnol. 2008 Jun;26(6):659-67
18536691
J Bacteriol. 2006 Feb;188(3):1175-9
16428423
J Bacteriol. 1996 Mar;178(5):1476-9
8631729
J Biol Chem. 1956 Jan;218(1):97-106
13278318
Biochemistry. 2008 Aug 5;47(31):8195-202
18616280
Biochemistry. 2003 Jan 14;42(1):80-9
12515541
J Bacteriol. 2008 Jul;190(13):4596-602
18441067
J Bacteriol. 2000 Sep;182(18):5180-7
10960103
J Bacteriol. 2000 Jan;182(1):228-32
10613887
J Biol Chem. 2004 Apr 23;279(17):17142-7
14769791
Annu Rev Biochem. 2009;78:569-603
19348578
Mol Syst Biol. 2006;2:62
17102807
J Bacteriol. 1999 Dec;181(23):7285-90
10572132
J Bacteriol. 1998 Feb;180(4):885-91
9473043
Org Biomol Chem. 2004 Sep 7;2(17):2538-46
15326535
J Bacteriol. 2004 Jun;186(12):4034-7
15175319
J Bacteriol. 2004 Nov;186(22):7626-34
15516576
J Bacteriol. 1991 Oct;173(20):6597-604
1917881
Biochemistry. 2009 Jan 20;48(2):217-9
19113839
Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13074-9
10557275
EMBO J. 2003 Sep 15;22(18):4826-35
12970194
J Bacteriol. 2008 Apr;190(8):3057-62
18296521
J Bacteriol. 2000 Jul;182(14):3896-903
10869064
Mol Gen Genet. 1993 Dec;241(5-6):602-15
8264535
J Bacteriol. 2006 Apr;188(8):3126-9
16585773
J Bacteriol. 1994 Aug;176(16):4858-64
7519593
J Bacteriol. 1997 Oct;179(20):6504-8
9335303
Nat Chem Biol. 2007 Apr;3(4):211-2
17334376
Proteins. 2006 Feb 1;62(2):557-61
16323205
Nat Rev Microbiol. 2008 Feb;6(2):156-61
18026122
J Bacteriol. 1998 Sep;180(17):4757-9
9721324
FASEB J. 2000 Mar;14(3):543-54
10698970
Genome Res. 2004 Nov;14(11):2367-76
15520298
J Biol Chem. 2004 Sep 24;279(39):40505-10
15271986
Genetics. 1996 May;143(1):37-44
8722760
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3266-71
15728363
J Biol Chem. 2010 Jan 1;285(1):583-94
19906644