Table 1.

Operon Structure and Predicted BirA Sites for the Biotin Biosynthetic Genes in Prokaryotes

Genome	AB	BirA		Biotin biosynthetic genes	Biotin transporters	Biotin-dependent caroxylases	BirA sites	Score	Pos
D-b	BPL
alpha-Proteobacteria
Caulobacter crescentus	CO	0	+	bioB / bioA <> bioF–bioD / bioC
Sinorhizobium meliloti	SM	0	+	bioC	cbiO–cbiQ–bioY–yhfT–yhfS
Mesorhizobium loti	MLO	0	+	bioB–bioF–bioD–bioA–bioZ / bioC	bioY1 / bioY2–X
Agrobacterium tumefaciens	AT	0	+	bioB–bioF–bioD–bioA–bioZ / bioC	cbiO–cbiQ–bioY
Rhodopseudomonas palustris	RPA	0	+	bioB / bioF–bioD–bioA / bioC	bioY–X–X
Bradyrhizobium japonicum	BJA	0	+	bioB / bioF–bioD–bioA / bioC	bioY–X–X
Rhodobacter capsulatus #	RS	0	+	bioB–bioF–bioD–bioA–bioG / bioC	cbiO1–cbiQ1–bioY1	madYZGB–birA–
					cbiO2–cbiQ2–bioY2	madAECDHKFLM
M. magnetotacticum #	MMA	0	+	[bioB bioF] / bioD–bioA / bioC
Brucella melitensis	BME	0	+	bioB–bioF–bioD–bioA–bioZ / bioC	bioY1 / bioY2-X
Rickettsia prowazekii	RP	0	+	none	bioY
beta-Proteobacteria
Bordetella pertussis #	BP	0	+	bioA <> bioF / bioB	cbiO–cbiQ–bioY
Burkholderia fungorum #	BU	0	+	bioA–bioF–bioD–bioB / bioC
Burkholderia pseudomallei #	BPS	−	+	bioA–bioF–bioD–bioB / bioC
Nitrosomonas europaea	NE	+	+	bioB–bioF–bioH–bioC–bioD / $ bioA			cTGTcttgC-(15)-GcTTgACAA	−246	5.99
Neisseria meningitidis	NM	−	+	bioB / bioH–bioC2 /bioF–bioG–bioC1 / bioA–bioD
Methylobacillus flagellatus #	MFL	+	+	$ bioB–bioF–bioH–bioC–bioD / bioA–X			aTGTAAAtg-(15)-GcTTgACAA	−68	7.10
Ralstonia solanacearum	RSO	0	+	bioA–bioF–bioD / X–X–bioB / bioC
Ralstonia eutropha #	REU	0	+	bioA–bioF–bioD–bioB / bioC
gamma-Proteobacteria
Escherichia coli	EC	+	+	bioA <$> bioB–bioF–bioC–bioD / bioH			TTGTAAACC-(16)-GGTTTACAA	−80	9.10
Salmonella typhi	TY	+	+	bioA <$> bioB–bioF–bioC–bioD / bioH			TTGTAAACC-(16)-GGTTTACgA	−80	8.49
Klebsiella pneumoniae #	KP	+	+	bioA <$> bioB–bioF–bioC–bioD / bioH			TTGTAAACC-(16)-GGTTTACAA	−207	9.10
Yersinia pestis	YP	+	+	bioA <$> bioB–bioF–bioC–bioD / bioH			TTGTAAACC-(16)-GGTTgACAg	−88	8.87
Vibrio cholerae	VC	+	+	bioA <$> bioB–bioF–bioC–bioD / bioH			aTGTAAACC-(15)-tGTTgACAg	−94	8.12
Francisella tularensis #	FT	+	+	bioA <$> bioB–bioF–bioC–bioD			TTGTAAACC-(15)-aGTTgACAt	−90	8.44
Legionella pneumophila #	LP	+	+	[bioA / [bioB–bioF–bioH–bioD / bioC
Haemophilus influenzae	HI	−	+	bioA–bioF–bioG–bioC–bioD / bioB
Haemophilus ducreyi #	DU	−	+	bioA–bioF–bioG–bioC–bioD / bioB
Pasteurella multocida	VK	−	+	bioA–bioF–bioG–bioC–bioD / bioB
A. actinomycetemcomitans #	AB	−	+	bioA–bioF–bioG–bioC–bioD / bioB
Pseudomonas aeruginosa	PA	+	+	$ bioB–bioF–bioH–bioC–bioD / bioA			aTGTAgtCC-(14)-GGTTgACAg	−130	7.43
Pseudomonas putida	Ppu	+	+	$ bioB–bioF–bioH–bioC–bioD / bioA			TTGTAAACC-(15)-aGTTgACAg	−125	8.47
Pseudomonas fluorescencs	PU	+	+	$ bioB–bioF–bioH–bioC–bioD / bioA			aTGTAAACC-(15)-GGTTgACAg	−128	8.71
Shewanella putrefaciens #	SH	+	+	bioA <$> bioB–bioF–bioC–bioD / bioH			TgGTAAACC-(15)-cGTTgACAg	−90	7.78
Thermochromatium tepidum #	CTE	+	+	$ bioB–bioF–bioH–bioC]/ [X–bioA			TTGTAAACC-(15)-aGTTgACAA	−112	8.60
Xylella fastidiosa	XFA	−	+	bioB / bioF–bioH / bioD / bioC / bioA
Acinetobacter calcoaceticus #	AC	0	+	bioB / bioH–bioA–bioF–bioC–bioD
Buchnera sp.	BUC	0	0	bioA <> bioB–bioD
epsilon-Proteobacteria
Helicobacter pylori	HX	0	+	bioA / bioD / X–bioF / bioC / bioB–X
Campylobacter jejuni	CJ	0	+	bioA <> bioF–bioG–bioC / X–bioD / X–bioB–X
Magnetococcus #	MCO	+	+	$ bioF–bioH–bioC1–bioB–X–bioD / bioA / bioC2			aaGTAAACC-(16)-aGTTgACtA	−46	7.44
Bacillus/Clostridium group
Bacillus subtilis	BS	+	+	$ bioW–bioA–bioF–bioD–bioB–biol			ATTGTTAAC-(15)-GTTAACAAT	−127	8.84
					$bioY1		tTTGTTAAC-(15)-GTTgACAAT	−89	8.54
					$bioY2–yhfT–yhfS		tATGTaAAC-(15)-GTTgACATa	−88	8.32
Bacillus sphaericus #	BW	?	?	$ bioD–bioA–bioY–bioB			tgTGTTAAC-(16)-GTTAACtAa	−52	7.86
				$ bioX–bioW–bioF			tgTGTTAAC-(15)-GTTAACtca	−67	7.49
Bacillus halodurans	HD	+	+	$ bioB			ATTGTTAAC-(15)-GTTtACAAT	−58	8.72
				$ bioD–bioA			tATGTTAAC-(15)-GTTAACATa	−42	8.64
				$ bioF–bioH–bioC			tATGTTAAC-(15)-GTTAACAAT	−68	8.74
					$ bioY		tATGTcAAC-(15)-GTTgACAAa	−89	8.24
							tATGTTAAC-(15)-GTaAACATT	−35	8.08
Bacillus stearothermophilus #	BE	+	+	$ bioY1–bioD–bioA / [bioB			AATGTaAAC-(15)-GTTgACAAa	−86	8.42
				$bioF			AATGTaAAC-(16)-GTTtACATa	−46	8.50
					$ bioY2		tTTGTTAAC-(15)-GTTtACATa	−33	8.52
Bacillus cereus	ZC	+	+	$ bioA–bioD–bioF–bioH–bioC–bioB			AATGTTAAC-(15)-GTTAACATT	−140	8.84
					$ bioY1		AATGTTAAC-(16)-GTTAACATT	−32	8.84
					$ bioY2–yhfT–yhfS		tTTGTaAAC-(15)-GTTgACAAa	−110	8.32
Clostridium acetobutylicum	CA	+	+	$ bioY1–bioD–bioA			ATTGTTAAC-(16)-GTTAACAAT	−44	8.84
		0	+	(D–b–birA) <$> bioY–bioB			ATTGTaAAC-(16)-GTTtACAAT	−44	8.60
					$ bioY2–X		ATTGTaAAC-(16)-GTTtACAAT	−19	8.60
Clostridium botulinum #	CB	+	+	[bioY–bioB–bioD	$ bioY		ATTGTTAAC-(16)-GTTgACAAT	−81	8.64
Clostridium difficile #	DF	+	+	$ bioB			tAaGTaAAC-(16)-GTTgACAAa	−44	7.91
							ATaGTaAAC-(16)-GTTgACcAa	−108	7.17
					$ bioY–yhfS–yhfT		AATGTaAAC-(16)-GTTgACAAa	−113	8.42
Clostridium perfringens	CP	+	+	$ bioY–bioB–bioD			ATTGTaAAC-(16)-GTTgACAAT	−127	8.52
				$ (D–b–birA)			ATTGTagAC-(16)-GTTgtCAAT	−133	6.82
Enterococcus faecalis	EF	+	+	none	$ bioY		ATTGTTAAC-(16)-GTTAACAAT	−49	8.84
Heliobacillus mobilis #	HMO	+	+	[bioD / [bioA	$ bioY		ATTGTcAAC-(16)-GTTgACAAT	−110	8.44
Kurthia sp. #	Kur	?	?	$ bioY–bioD–bioA			tATGTTAAC-(14)-GTTgACATa	−101	8.44
				$ orf2–bioF–bioB			tATGTTAAC-(14)-GTTAACATa	−55	8.64
				$ bioF–bioH–bioC / bioH			tATGTTAAC-(14)-GTTAACATa	−50	8.64
Listeria innocua	LI	+	+	none	$ bioY		AATGTTAAC-(15)-GTTtACATT	−178	8.72
Lactococcus lactis	LL	+	+	none	(D–b–birA)–bioY <$> yhfT–yhfS		AcaGTTAAC-(16)-GgTtACtgT	−98	6.48
		0	+		bioY
Staphylococcus aureus	SAX	+	+	$ bioD–bioA–bioB–bioF–bioW–bioX			AATGTaAAC-(15)-GTTtACATT	−56	8.60
					$ bioY		ATTGTaAAC-(15)-GTTtACAAT	−74	8.60
					$ yhfT–yhfS		AATGTTAAC-(15)-GTTtACATT	−49	8.72
Streptococcus pneumoniae	PN	+	+	none	$ bioY		tTTGTTAcC-(16)-GTTgACATc	−86	7.41
Steptococcus pyogenes	ST	+	+	none	$ bioY		AcaGTTAcC-(16)-GTTgACAAa	−72	7.14
					$ yhfS–yhfT		AAaGTcAcC-(16)-GgTtACAgT	−270	6.56
Streptococcus equi #	SEQ	+	+	none?	$ bioY		gTTGTcAAC-(15)-GgTAgCAAT	1	6.66
					$ yhfS–yhfT		AAaGTTAAC-(16)-GgTtACAAT	−567	7.75
Actinobacteriae
Corynebacterium glutamicum #	CGL	0	+	bioB / bioA–bioD	bioY–cbiO–cbiQ	birA <> pccB1–pccB2
Corynebacterium diphtheriae #	DI	0	+	bioB1 / bioA–bioD / bioW–bioF / bioB2	bioY–cbiO–cbiQ	birA <> pccB
Mycobacterium tuberculosis	MT	0	+	bioB / bioA–bioF–bioD		birA <> pccB–X–X–X–pccA
Streptomyces coelicolor #	SX	0	+	bioF <> bioB–bioA–bioD	bioY	birA <> pccB–X–X–pccA
Thermomonospora fusca #	TFU	0	+	none?	bioY–cbiO–cbiQ	birA–ppc <> pccB–pccA
CFB/Green sulfur bacteria group
Bacteroides fragilis #	BX	0	+	bioA–bioF–bio(GC)–bioD
Cytophaga hutchinsonii #	CHU	0	+	bioB / bioF–bioD–bioA
Porphyromonas gingivalis #	PG	0	+	bioB–bioA] / X–bioD / bioG–bioC / bioF]
D-b	BPL
Cyanobacteria
Nostoc sp.	NPU	0	+	bioB / bioD / bioF / bioA	bioY–lspA
Synechocystis sp.	CY	0	+	bioB–bioY–IspA / bioD / bioF / bioA
Prochlorococcus marinus	CK	0	+	X–X–bioB / bioF–X–bioC–bioD–bioA	bioY–IspA
Synechococcus sp.	SN	0	+	X–X–bioB / bioF–X–bioC–bioD–bioA	bioY–IspA
Others
Aquifex aeolicus	AA	0	+	X–X–bioB / bioW–X–X / X–X–bioD / bioA / bioC
Chlamydia trachomatis	QT	0	+	bioB–bioF–bioD–bioA–bioW	bioY
Chlorobium tepidum	CL	+	+	$ birA–bioB–bioF–bioG–bioC–bioD–bioA–fadD			TTGTcAACC-(14)-GGTTTACAA	−143	9.00
Chloroflexus aurantiacus #	CAU	0	+	none	bioY
Deinococcus radiodurans	DR	−	+	none	bioY–cbiO–cbiQ
Fusobacterium nucleatum #	FN	0	+	bioB–bioD–bioA / bioF–bioG–bioC
Thermotoga maritima	TM	0	+	none	fabH–fabZ–fabK–bioY–fabD
Thermus thermophilus #	TQ	+	+	$ bioB			TcGTAAACt-(15)-GGTTTACgA	21	7.48
					$ bioY		acGTcAACC-(15)-GGTTgACgA	615	7.52
Treponema pallidum	TP	0	+	none	bioY–cbiO–HTP1
Archaea
Archaeoglobus fulgidus	AG	+	+	none	$ bioY–cbiO–HTP2		cTcGTTAAC-(15)-GTTAACgAT	−22	6.39
						$ pycA	gcTGTaAAt-(16)-GaTAACAAT	−173	6.03
Halobacterium sp.	HSL	+	+	none	$ bioY–cbiO–HTP3		gTcGTaAAC-(16)-GTTgACgAc	−50	5.70
		0	+			pccB–pccA–X–$(D–b–birA)	tAaaTaAAC-(14)-GTTgAgtTa	−118	5.80
M. thermoautotrophicum	TH	0	+	none	bioY	pycA–birA
Methanococcus jannaschii	MJ	0	+	bioB1 / bioB2 <> bioW–bioF–bioD–bioA
Methanosarcina barkeri #	MBA	+	+	none?	$ bioY–cbiO–cbiO–cbiQ		AATGTaAAC-(16)-GTTAACAAT	−275	8.72
						$ pycB–pycA–(D–b–birA)	gTaGTTcAC-(16)-GTTAACAgg	−365	5.81
Methanosarcina mazei	MMZ	+	+	none	$ bioY–cbiO–cbiO–cbiQ		AATGTaAAC-(16)-GTTAACAAT	−269	8.72
						$ pycB–pycA–(D–b–birA)	AAcGgcAgC-(15)-GTTAACAAT	−349	6.11
Pyrococcus abyssii	PO	+	+	none	bioY <$> (D–b–birA)		tTcGTTAAC-(16)-GTTAACcAa	−43	6.96
		0	+
Pyrococcus furiosus	PF	+	+	none	bioY > (D–b–birA)		gTgGTTAAC-(16)-GTTACgAa	−55	6.49
		0	+
Pyrococcus horikoshii	PH	0	+	none	bioY
Sulfolobus solfataricus	STO	0	+	none

The genome abbreviations are given in column AB. Unfinished genomes are marked by #. The names of taxonomic groups are given in bold. The signs + and 0 in the columns “BirA D–b” and “BirA BPL” denote the existence or absence of the N-terminal regulatory domain (D-b) and C-terminal catalytic domain (BPL) of BirA, respectively; − denotes N-terminal BirA domain not similar to the known regulatory BirA domain. Other columns show the operon structure and regulation of the biotin-related genes. Genes forming one candidate operon (with spacer <100 bp) are separated by dashes. Different loci are separated by slashes. The direction of transcription in divergons is shown by angle brackets. Predicted BirA sites are denoted by $. The contig ends are shown by square brackets. Bio(GC) is the fusion of the bioG and bioC genes. HTP1, HTP2, and HTP3 are nonhomologous hypothetical transmembrane proteins clustered with bioY–cbiO. The other genes of unknown function are denoted by X. The birA genes are shown only if they are colocalized with other biotin-related genes. The positions of the site are given relative to annotated translation starts. The site scores are computed using positional nucleotide weight matrices of two types, proteobacterial and nonproteobacterial, as described in Methods. The BirA sites of the proteobacterial type are given in bold.