onpathway: connectivity on pathway map; The single or multi represents a single-step reaction like C1->C2 or a multi-step like C1->->C2, respectively.

annotated: EC sub-subclass with indicating either single-step or multi-step reaction; They are assumed from the reaction equation and the compound structures involved in. The EC number assignment process we performed here complies with the EC number classification scheme. When the third digits of annotated EC numbers are hyphens, they mean that we need more detailed information about cofactors to decide which one is best.

=========================================================

C02362=>C06625
onpathway: single # map00253, R05457
annotated: multi [4.1.1 + 2.6.3]
 After eliminating a carbon dioxide from C02362 (4.1.1), the other group of C02362 will be transferred to CoA (2.6.3).
by_E-zyme: 1.2.7:1.0

C06069=>C06070
onpathway: single # map00900, R05089, incomplete reaction
annotated: single [1.13.- or 1.14.-]
 One -CH3 group in C06069 will be oxidized to form aldehyde -CHO like methane mono-oxygenase. Another compound may be required as donor.
by_E-zyme: 1.17.99:3.5 1.14.-:0.5

C01221=>C01138
onpathway: single # map00521, R05515
annotated: single [1.1.1]
 This is an oxidation of alcohol -OH to aldehyde =O with NAD+ as cofactor.
by_E-zyme: 1.14.13:100.7 1.14.11:19.2 1.14.15:18.4 1.14.14:16.4 1.14.16:4.5 1.14.-:4.2 1.17.99:3.8 1.14.99:2.7 1.14.18:1.6 1.97.1:1.1 1.3.99:1.0 1.13.12:0.9 1.10.99:0.7 1.13.11:0.4 1.10.3:0.3

C06179=>C00783
onpathway: single # map00960, R06733, multi-step reaction
annotated: single [4.1.99] # maybe single-step
 C-C single bond is formed to a cyclized C06179. At the same time, another molecule, that is, one hydrogen molecule will be produced.
by_E-zyme: NA

C06178=>C06179
onpathway: single # map00960, R06732, multi-step reaction
annotated: single [4.1.99] # maybe single-step
 Some atom group (*-CH2COCH3) will attack at the C=N double bond in C06178. Reaction equation is incomplete, but it may occur at single-step.
by_E-zyme: NA

C01456+C00729=>C02046
onpathway: single # map00960, R03564
annotated: single [3.1.1]
 Structures of C02046 and C01479 are almost the same except structural isomerism. Thus, a hydrolysis will also occur at a carboxylic-ester bond, like R03563, which is assigned as 3.1.1.10.
by_E-zyme: 6.1.1:27.0 3.1.1:8.0

C06175=>C01735
onpathway: single # map00950, R03698, incomplete reaction
annotated: multi [2.1.1 + 1.1.1]
 After removing a methyl group of C06175 (2.1.1), C01735 will be produced by oxidation of CH-OH group (1.1.1). In the second reaction, NAD+/NADP+ will be probably used as acceptor.
by_E-zyme: 2.1.1:492.4 1.13.12:23.9 1.14.14:12.3 3.1.1:7.0 1.5.3:4.0 1.5.99:3.0 1.14.13:2.7 1.1.1:2.0 1.2.3:2.0 1.5.8:2.0 1.14.99:1.0 2.3.1:1.0 1.16.1:1.0

C01860=>C06080
onpathway: multi # map00900, R03740, multi-step & incomplete reaction
annotated: multi [-]
 This reaction may involve a series of oxidation reactions, however, the actual change between both sides is complicated and thus to guess any EC number is impossible.
by_E-zyme: NA

C05838=>C05851
onpathway: single # map00940, R04999, non-enzymatic reaction
annotated: non-enzymatic [1.13.- or 1.14.-]
 The intra-molecular reaction can be occurred without any enzymes. This is the proximity effect between hydroxyl group and carboxyl group, which forms C-O-C bond and one water molecule. This reaction activity is like that of mono-oxygenase; 1.13.- or 1.14.-.
by_E-zyme: 1.14.12:53.2 1.14.14:6.2 1.14.99:3.5 1.13.11:2.3 1.14.-:2.1 1.14.13:0.7 1.3.1:0.5

C06071=>C01433
onpathway: single # map00900/901, R03556, already assigned as 1.14.13.74
annotated: single [1.14.13]
 Mono-oxygenation occurs and one atom of oxygen is incorporated into C01433 with NADPH as a donor.
by_E-zyme: 1.14.13:26.8 1.14.11:24.2 1.14.15:17.9 1.14.14:7.8 1.14.-:4.4 1.17.99:3.4 1.14.99:1.5 1.13.12:0.7 2.5.1:0.2

C06366=>C12440
onpathway: single # map00960, R06724
annotated: multi [4.3.1 + 1.14.13 + 4.1.99]
 The total reaction involves two eliminations of -NH2 (4.3.1), one addition of -OH via oxidation (1.14.13), and two ring formations (4.1.99), indicating that this reaction may be multi-step.
by_E-zyme: NA

C06067=>C06068
onpathway: multi # map00900, R05088, multi-step reaction
annotated: multi [5.4.1 + 5.4.4 + 4.3.99]
 The total reaction can be described as an elimination of one water molecule from C06067. However, this involves two intra-molecular transferase, that is, one methyl group (5.4.1) and one oxygen atom (5.4.4) are transferred. After that, the ring formation is also occurred (4.3.99).
by_E-zyme: NA

C06181=>C00431
onpathway: single # map00310
annotated: multi [3.5.2 + 1.1.-]
 There are two reaction activities; one is to break a C-N single bond of C06181 (3.5.2), and another is to oxidize a hydroxyl group with a cofactor (1.1.-).
by_E-zyme: NA

C06070=>C06071
onpathway: multi # map00900, R05090, multi-step & incomplete reaction
annotated: multi [2.4.1 + ?]
 The hexose group is attached to C06070. The intra-molecular epimerization will also take place. The latter reaction is too complicated to assign a proper EC sub-subclass.
by_E-zyme: NA

C01494=>C01752
onpathway: multi # map00940, R03580, multi-step & incomplete reaction
annotated: multi [1.14.- + 2.4.1 + 5.2.1 + 3.2.1]
 This is not a simple reductase reaction, but this reaction is thought to be a set of 4 enzymatic and 1 non-enzymatic reactions by analogy with the similar pathway C00423 => C01772 => C05158 => C05839 => C05838 => C05851. Here, the last reaction (C05838 => C05851) is spontaneous.
by_E-zyme: NA

C06625+C00083=>C06629
onpathway: single # map00253, R05464, probably multi-step reaction
annotated: multi [2.3.1]
 This is one of typical synthetic reactions of polyketide, which usually involves several acyl-transferase activities in one reaction. Here, 9 acyl-transferase reactions (2.3.1) may take place.
by_E-zyme: NA

C06181=>C06182
onpathway: single # map00960, R05129
annotated: single [3.1.2 + 4.1.1 + 2.2.1]
 This is an ordinary transferase reaction (2.2.1), but a hydrolysis (3.1.2) and an elimination of carbon dioxide (4.1.1) are also included.
by_E-zyme: NA

C06628=>C06627
onpathway: single # map00253, R05462
annotated: multi [1.13.12 + 1.1.1]
 Mono-oxygenase activity may occur with a water molecule as donor. And the oxidation to form aldehyde take place with NADPH as cofactor.
by_E-zyme: NA

C12440=>C06177
onpathway: single # map00960, R06725
annotated: single [1.13.- or 1.14.-]
 Mono-oxygenase reaction may occur, however the donor is unclear.
by_E-zyme: NA

C02646=>C12206
onpathway: single # map00940, R06580
annotated: single [1.14.-]
 This reaction is thought to be 1.14.- by analogy with three reactions, C05608=>C10945, C00223=>C00323, and C00811=>C01197, which are catalyzed by C3H (p-coumarate 3-hydroxylase) (1.14.-).
by_E-zyme: 1.14.13:231.7 1.14.14:13.8 1.14.16:8.9 1.14.15:8.7 1.14.11:7.3 1.14.18:5.0 1.14.99:4.6 1.13.11:2.0 1.3.99:2.0 1.97.1:2.0 1.10.99:1.9 1.17.99:1.9 1.14.-:1.1 1.10.3:1.0 1.13.12:0.9 1.14.12:0.5 1.1.3:0.5 1.17.3:0.5 1.14.17:0.5

C00806+C00235=>C06067
onpathway: single # map00900,  R02943, already assigned as 2.5.1.34
annotated: single [2.5.1]
 2-Isopentenyl group of C00235 will be transferred to benzene ring of C00806.
by_E-zyme: 2.5.1:123.7

C03206=>C06570
onpathway: single # map00253, R05459
annotated: single [1.1.1]
 This reaction is an oxidation of CH-OH using NAD+ as cofactor.
by_E-zyme: NA

C02105=>C06167
onpathway: single # map00950, R03833
annotated: single [1.5.-]
 The chemical structures of C02105 and C05178 are almost the same except structural isomerism. Thus, an oxidation will be occurred on the CH-NH group, like R04695. No cofactor information could be obtained.
by_E-zyme: 1.5.1:61.9 1.4.3:2.0 1.4.1:1.0 2.5.1:1.0 1.5.-:1.0 1.5.7:1.0 1.5.99:0.2

C06182=>C06183
onpathway: single # map00960, R05130
annotated: single [4.1.99]
 C-C single bond will be generated to form C06183.
by_E-zyme: 2.3.1:240.7 6.2.1:32.4 3.1.2:27.9 3.1.1:16.6 4.1.2:14.9 1.2.1:13.8 4.1.3:13.0 2.5.1:11.2 2.3.3:9.8 4.1.1:8.6 4.4.1:6.2 3.7.1:6.0 1.14.99:6.0 6.4.1:5.9 2.1.3:4.7 2.1.1:3.9 1.2.7:3.7 1.1.1:3.6 2.8.1:2.9 2.3.2:2.7 6.1.1:2.5 1.8.1:2.4 1.14.18:2.0 1.14.-:1.4 1.2.4:1.4 3.5.1:1.4 3.2.1:1.2 3.11.1:1.0 1.14.12:1.0 4.2.1:0.9 1.13.11:0.9 2.8.3:0.9 2.1.2:0.6 1.2.3:0.5 2.6.1:0.5 4.5.1:0.5 3.3.1:0.5 1.8.3:0.5 2.3.-:0.5 1.-.-:0.2

C<=>C06514
onpathway: single # map00950
annotated: single [4.2.99]
 C-O bond is formed and a hydrogen molecule is produced.
by_E-zyme: NA

C05322=>C06173
onpathway: single # map00950, R04769, spontaneous
annotated: non-enzymatic [4.2.99]
 The acetate group will be removed without any enzymes. This reaction has the same property of EC 4.2.99.
by_E-zyme: NA

C06173=>C06175
onpathway: single # map00950, R05127
annotated: single [2.1.1 or 1.14.14]
 This reaction is the same reaction with the first part of C06175=>C01735. Then, this is a reverse activity of methyl-transferase (2.1.1). However, if this is the same with other compound pair like C06174=>C01516, then this is one of oxidations performed by CYP (1.14.14). Since the reaction equation is incomplete, this reaction can be assumed as both EC sub-subclasses.
by_E-zyme: 2.1.1:489.0 1.14.14:9.5 3.1.1:6.6 1.5.3:4.0 1.5.99:3.0 1.2.3:1.6 1.14.99:1.0 1.14.13:1.0 1.16.1:1.0 2.3.1:0.5

C06172=>C06171
onpathway: single # map00950, R05125
annotated: single [5.3.3]
 The replacement of a C=C double bond is occurred within a molecule.
by_E-zyme: 1.3.1:124.6 1.3.99:52.9 5.3.3:16.2 1.3.3:14.2 2.3.1:12.6 1.14.11:8.4 1.14.99:6.8 1.3.-:4.4 1.14.21:2.0 1.2.1:1.6 1.1.-:1.5 1.14.-:1.0 5.2.1:1.0 1.14.14:1.0 1.14.12:1.0 1.18.-:0.8 1.1.3:0.6 1.3.5:0.5

C00448=>C06081
onpathway: multi # map00900, R02308, incomplete reaction
annotated: single [3.1.7]
 This is a simple hydrolysis reaction to remove a diphosphate.
by_E-zyme: 2.7.1:406.4 3.1.3:122.6 3.6.1:74.0 2.7.4:57.8 2.7.8:54.2 3.6.3:34.3 2.7.7:30.9 2.7.11:30.1 3.1.4:27.0 2.7.2:11.8 2.7.6:9.7 2.7.3:8.7 3.6.4:7.4 4.6.1:5.3 3.1.7:5.0 2.7.9:4.7 3.6.5:4.0 3.2.1:3.0 2.7.12:2.7 2.7.13:2.3 4.1.1:2.0 2.6.-:2.0 2.7.-:1.7 2.7.10:1.3 1.3.99:1.3 1.18.6:1.3 4.2.3:1.0 3.1.5:1.0 2.7.99:1.0 2.4.1:1.0 5.1.3:1.0 1.19.6:0.7

C00745=>C06524
onpathway: single # map00960, R06738
annotated: single [2.1.1]
 Methylation will take place.
by_E-zyme: 2.1.1:484.2 1.14.14:10.0 3.1.1:5.9 1.5.3:4.0 1.5.99:3.0 1.2.3:1.3 1.14.13:1.0 1.14.99:1.0 1.16.1:1.0 2.3.1:0.3

C04712=>C15666
onpathway: single # map00311, R07401
annotated: single [4.1.1 + 1.11.1]
 This reaction is an oxidation of -CHOH to -COOH using peroxide (1.11.1), following an elimination of carbon dioxide (4.1.1).
by_E-zyme: 1.13.11:122.5 1.13.-:1.5 2.8.1:1.1 3.7.1:0.5 1.97.1:0.5

C01294=>C01121
onpathway: multi # map00521, R05514
annotated: single [2.1.4]
 An amidine group, that is, -C=NH-NH2, is transferred to C01294.
by_E-zyme: 3.2.2:35.9 2.6.99:3.9 2.4.2:3.1 2.4.1:1.3 4.3.3:0.4

C00407+C06177=>C06176
onpathway: single # map00960, R06726
annotated: multi [-]
 The detailed of this reaction cannot be assumed because of incompleteness of reaction equation. But, this reaction may be multi-step. 
by_E-zyme: NA

C06181=>C01513
onpathway: multi # map00960, R06739, multi-step reaction
annotated: multi [-]
 There is no clue to guess any EC numbers, because of incompleteness of reaction equation.
by_E-zyme: NA

C06173=>C06172
onpathway: single # map00950, R05126
annotated: multi [2.1.1 + 1.1.1]
 This is the similar reaction with R03698, whose pair is C06175=>C01735.
by_E-zyme: 2.1.1:492.4 1.13.12:23.9 1.14.14:12.3 3.1.1:7.0 1.5.3:4.0 1.5.99:3.0 1.14.13:2.7 1.1.1:2.0 1.2.3:2.0 1.5.8:2.0 1.14.99:1.0 2.3.1:1.0 1.16.1:1.0

C10858=>C12449
onpathway: single # map00960, R06730
annotated: single [5.1.2]
 This is one of epimerases, which changes chirality around carboxyl group.
by_E-zyme: 5.1.-:1.0

C03206=>C06624
onpathway: single # map00253, R05461
annotated: multi [1.1.- + 1.14.-]
 Mono-oxygenase activity and oxidation of C-OH are needed. But neither donors nor cofactors are clear.
by_E-zyme: NA

C01672=>C06181
onpathway: multi # map00960, R03666, =R06740+R06741, partially assigned as 1.4.3.21
annotated: multi [1.4.3 + 3.5.4]
 There are two reactions; deamination via oxidation (1.4.3) and cyclic amidine formation (3.5.4).
by_E-zyme: NA

C06629=>C06628
onpathway: single # map00253, R05463
annotated: single [1.13.- or 1.14.-]
 This is mono-oxygenase.
by_E-zyme: 1.14.13:233.5 1.14.14:15.4 1.14.15:9.3 1.14.16:8.9 1.14.11:7.5 1.14.99:6.1 1.14.18:5.0 1.13.11:2.0 1.97.1:2.0 1.3.99:2.0 1.10.99:1.9 1.17.99:1.9 1.14.-:1.1 1.10.3:1.0 1.13.12:0.9 1.14.12:0.4 1.1.3:0.4 1.17.3:0.4 1.14.17:0.4

C00423=>C01416+C01456
onpathway: multi # map00960, R06745(423<->1416), R06744(423<->1456)
annotated: multi [2.6.99 + ?]
 This can be divided into two parts: C00423=>C01416 and C00423=>C01456. The former reaction is a transferase reaction of a large substructure including methyl-pyrrole ring (2.6.99). The latter includes epimerase reaction and oxidation, but no clue is available to assign one of EC sub-subclasses.
by_E-zyme: NA

C12455=>C06181
onpathway: single # map00960, R06741
annotated: single [3.5.4]
 This is the latter part of C01672=>C06181.
by_E-zyme: NA

C00137=>C01214
onpathway: single # map00521, R05513, =R01183+R02781
annotated: multi [1.1.1 + 2.6.1]
 After oxidation reaction of CH-OH to aldehyde with NAD+ (1.1.1), an amino group will be transferred like R00576 (2.6.1).
by_E-zyme: 2.6.1:95.5 1.4.1:16.3 1.4.3:9.4 6.3.4:2.0 4.3.1:0.8 1.4.99:0.8 1.4.7:0.5 3.5.3:0.2 4.1.1:0.2

C06180=>C12454
onpathway: single # map00960, R06743
annotated: single [2.6.99]
 The pyridine group is transferred to C06180 from something.
by_E-zyme: 1.14.13:205.1 1.14.14:16.1 1.14.99:16.0 1.14.11:12.7 1.14.15:11.3 1.14.16:9.0 1.14.18:7.8 1.14.-:4.6 1.17.1:4.2 1.14.12:4.0 1.17.4:3.2 1.3.99:3.0 1.17.99:2.3 1.97.1:2.0 1.13.11:2.0 1.-.-:1.8 1.7.1:1.7 1.1.4:1.7 1.10.99:1.7 1.17.3:1.5 1.6.6:1.1 1.10.3:1.0 1.13.12:0.9 1.1.-:0.9 1.14.17:0.9 3.8.1:0.8 1.1.1:0.5 1.1.99:0.4 1.17.-:0.4 1.8.99:0.4 1.4.-:0.4 3.5.99:0.3 4.2.1:0.3

C01433=>C01852
onpathway: single # map00901, R03555, already assigned as 1.3.3.9
annotated: single [1.3.3]
 This is an oxidoreductase on the CH-CH group of donors with oxygen as acceptor.
by_E-zyme: NA

C04767+C06592=>C01221
onpathway: single # map00521, R06365
annotated: single [2.4.1]
 This is one of NDP-glycosyltransferases. Here, N-methyl-L-glucosamine is a transferred group.
by_E-zyme: 3.2.1:89.9 2.3.1:4.0 2.4.1:1.0 4.2.-:1.0 1.-.-:0.5

C00751=>C06083
onpathway: multi # map00900, R02875, multi-step reaction
annotated: single or multi [4.2.1]
 After addition of one water molecule (4.2.1), displacements of electrons are occurred within a molecule. No intermediates can be obtained.
by_E-zyme: NA

C05190=>C05191
onpathway: single # map00950, R04701, incomplete reaction
annotated: non-enzymatic [5.3.99]
 Two water molecules will be removed without any enzymes. This reaction is similar with an intra-molecular reductase reaction like 5.3.99.
by_E-zyme: NA

C05177=>C06513
onpathway: single # map00950
annotated: single [4.2.99]
 To form O-C bond will cause a following ring formation.
by_E-zyme: 4.2.1:155.5 1.1.1:13.4 2.3.1:12.0 1.13.11:11.9 4.3.1:9.8 4.5.1:3.1 4.3.2:3.0 4.2.2:2.8 4.1.3:2.6 4.1.99:2.0 4.1.2:1.9 1.14.11:1.8 4.3.3:1.2 3.5.1:1.0 1.1.-:1.0 4.2.99:1.0 2.2.1:0.9 4.2.3:0.9 4.4.1:0.9 4.1.1:0.8 1.14.13:0.7 1.13.99:0.5 1.11.1:0.4

C06111=>C01860
onpathway: multi # map00900, R03741
annotated: multi [3.1.7 + ?]
 Diphosphate is removed. After that, two intra-molecular ring formations take place. The latter part is too complicated to guess any EC.
by_E-zyme: NA

C00408=>C06185
onpathway: multi # map00960, R06742, maybe =R08415+R08417, incomplete
annotated: multi [-]
 This involves two reactions; one is a ring formation, which requires at least two carbons, another is two transferase reactions, where CH3-C=O-NH-* and CH3-C=O-* are transferred from something.
by_E-zyme: NA

C00341=>C06069
onpathway: multi # map00900, R02008
annotated: multi [3.1.7 + ?]
 Diphosphate is removed. After that, two oxidations or mono-oxygenase reactions take place.
by_E-zyme: NA

C06626=>C06571
onpathway: single # map00253, R05460
annotated: multi [2.6.99 + 2.1.1 + 1.13.12]
 An amino group will be transferred to C06571, and then two methyl groups <will be attached. Finally, mono-oxygenase reaction will occur with an oxygen molecule as donor.
by_E-zyme: NA

C00047=>C00408
onpathway: single # map00960, R00459, =R00715+R02313+R02317+R08414
annotated: multi [1.4.3 + 4.2.1 + 1.5.1 + 1.5.1]
 On map00310, the multi-step reactions of this reaction are drawn. In that case, this reaction is a series of four enzymatic reactions like 1.5.1.7 + 1.5.1.9 + 1.4.1.18 (deamination) + reductase around N atom. The last reaction seems 1.5.3.7 or 1.5.99.3, whose differences are depending on donors.
by_E-zyme: 1.8.1:11.8 2.6.1:3.1 2.5.1:1.0 1.8.4:1.0

C02066=>C10850
onpathway: multi # map00960, R06737, multi-step reaction
annotated: multi [1.14.- + 2.1.1]
 Demethylation and di-oxygenation will take place.
by_E-zyme: NA

C06568=>C06569
onpathway: single # map0311, R05302
annotated: single [1.14.20]
 This is one of oxidoreductases acting on C06568 and 2-oxoglutarate.
by_E-zyme: 1.14.99:21.6 1.14.13:14.6 1.14.14:2.9 1.14.15:2.5 1.14.12:2.0 1.-.-:1.6 4.1.2:1.2 1.14.11:1.2 2.1.1:0.9 1.14.18:0.6 1.17.1:0.6 1.1.-:0.6 1.14.-:0.5 1.13.12:0.4 1.17.99:0.3

C06174=>C01516
onpathway: single # map00950, R03697, already assigned as 1.14.14.1
annotated: single [1.14.14]
 This reaction activity is known as the O-demethylation of CYP2D6.
by_E-zyme: 2.1.1:489.0 1.14.14:9.5 3.1.1:6.6 1.5.3:4.0 1.5.99:3.0 1.2.3:1.6 1.14.99:1.0 1.14.13:1.0 1.16.1:1.0 2.3.1:0.5

C06182=>C06184
onpathway: single # map00960, R05131, incomplete reaction
annotated: single [2.1.1]
 Methyl group will be transferred from somewhere.
by_E-zyme: 2.1.1:484.2 1.14.14:10.0 3.1.1:5.9 1.5.3:4.0 1.5.99:3.0 1.2.3:1.3 1.14.13:1.0 1.14.99:1.0 1.16.1:1.0 2.3.1:0.3

C03319=>C03442
onpathway: single # map00521, R05516
annotated: single [5.3.1]
 This is an intra-molecular isomerase reaction. Here, a mannose is changed to one of branching hexose, streptose.
by_E-zyme: NA

C06178+C00180=>C01416
onpathway: multi # map00960, R06727
annotated: multi [-]
 This is an incomplete and very complicated reaction, indicating that it is multi-step.
by_E-zyme: NA

C00253=>C10126
onpathway: single # map00960, R06779
annotated: single [4.1.1]
 C-C bond formation with a production of carbon dioxide will take place.
by_E-zyme: 1.13.99:1.5 4.2.1:0.5