S1. The Carbocation Library

Our carbocation numbering system uses a four-tier hierarchical classification, SiteType ID + CarbonNumber + ReactionChannel ID + Intermediate ID: 1) the active site type, i.e. Site-I dephosphorylation or Site-II protonation; 2) number of carbon atoms; 3) reaction channels; 4) the carbocation intermediates. For example, R01.010.A01.01 means Site-I type reaction (dephosphorylation), C10 substrate and product (Figure S1-1), reaction channel A01 (in reaction channel ID A01, ‘A’ is the first classification of the reaction channel, e.g. 1,6 cyclization, ‘01’ is the second classification of the reaction channel). Descriptions of the current reaction channels are listed in Table S1-1. 2D formulas of the reaction channels and carbocation structures and the EC numbers covered by each intermediate are shown in Table S1-2 (Site-I channels) and Table S1-3 (Site-II channels).

The attribute ‘representative intermediate’ describes if an intermediate is a representative intermediate for reaction channel prediction. We normally select two representative intermediates for one reaction channel, which are used to describe the first major transition state leading to product diversity. In the Site-I type reactions, the first representative intermediate is the dephosphorylated carbocation that is about to be cyclized, for example, in reaction channel R01.010.A01 (Table S1-2-1), the first representative intermediate is R01.010.A01.02, rather than R01.010.A01.01, because 1,6 cyclization requires the rotation of the C2-C3 double bond; the second representative intermediate is the first cyclized carbocation intermediate, e.g. R01.010.A01.03. In the Site-II type reactions, the first and the second representative intermediates are the (6,6) and (6,6,6,5) species. The representative intermediates are highlighted with red color in the reaction schemes. Most of the reaction channels were summarized in a recent review by Tantillo, D. J. 1 and the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (IUBMB, http://www.chem.qmul.ac.uk/iubmb/).


Figure S1-1. Illustration of the carbocation library numbering system

image1.tif

Table S1-1a. Description of different reaction channels

Reaction Channel ID

Substrate

Mechanism Description

EC numbers covered by the channel

References

R01.010.A01

GPP

GPP 1,6 cyclization

 4.2.3.20; 4.2.3.108; 4.2.3.112; 4.2.3.113; 4.2.3.121; 4.2.3.122; 5.5.1.8; 4.2.3.116; 4.2.3.114; 4.2.3.115; 4.2.3.11; 4.2.3.109; 4.2.3.110; 4.2.3.10

2-6

R01.010.A02

GPP

GPP 1,6 cyclization

4.2.3.16; 4.2.3.107; 4.2.3.111; 4.2.3.113; 4.2.3.119; 4.2.3.120; 5.5.1.22; 4.2.3.117; 4.2.3.105; 4.2.3.52; 4.2.3.114; 4.2.3.115; 4.2.3.109; 4.2.3.110

2-6

R01.011.A01

C11GPP

GPP 1,6 cyclization

4.2.3.118

7, 8

R01.011.A02

C11GPP

GPP 1,6 cyclization

 

7, 8

R01.015.A01

FPP

FPP 1,6 cyclization

4.2.3.38;4.2.3.40;4.2.3.59; 4.2.3.95; 4.2.3.6

9, 10

R01.015.A02

FPP

FPP 1,6 cyclization

 4.2.3.38;4.2.3.40;4.2.3.55;4.2.3.59;4.2.3.138; 4.2.3.82; 4.2.3.81; 4.2.3.83; 4.2.3.69; 4.2.3.78; 4.2.3.79

9, 10

R01.015.A03

FPP

FPP 1,6 cyclization

4.2.3.38;4.2.3.40;4.2.3.59; 4.2.3.94; 4.2.3.37; 4.2.3.50; 4.2.3.102

11

R01.015.A04

FPP

FPP 1,6 cyclization

4.2.3.38;4.2.3.40;4.2.3.55;4.2.3.59;4.2.3.138; 4.2.3.53; 4.2.3.54; 4.2.3.101

11

R01.015.A05

FPP

FPP 1,6 cyclization

4.2.3.38;4.2.3.40;4.2.3.59; 4.2.3.94; 4.2.3.24

12, 13

R01.015.A06

FPP

FPP 1,6 cyclization

4.2.3.38;4.2.3.40;4.2.3.55;4.2.3.59;4.2.3.138; 4.2.3.65; 4.2.3.123; 4.2.3.142

12, 13

R01.015.A07

FPP

FPP 1,6 cyclization

4.2.3.38;4.2.3.40;4.2.3.59

14

R01.015.A08

FPP

FPP 1,6 cyclization

 4.2.3.38;4.2.3.40;4.2.3.55;4.2.3.59;4.2.3.138; 5.5.1.17

14

R01.015.A09

FPP

FPP 1,6 cyclization

4.2.3.38;4.2.3.40;4.2.3.59

11

R01.015.A10

FPP

FPP 1,6 cyclization

 4.2.3.38;4.2.3.40;4.2.3.55;4.2.3.59;4.2.3.138; 4.2.3.39

11

R01.015.B01

FPP

FPP 1,10-trans cyclization

 4.2.3.22;4.2.3.23;4.2.3.60;4.2.3.71; 4.2.3.90; 4.2.3.61; 4.2.3.21; 4.2.3.93; 4.2.3.87

15, 16

R01.015.B02

FPP

FPP 1,10-trans cyclization

4.2.3.60;4.2.3.71

15, 16

R01.015.B03

FPP

FPP 1,10-trans cyclization

4.2.3.22;4.2.3.23;4.2.3.60;4.2.3.71; 4.2.3.66; 4.2.3.76; 4.2.3.70

17-20

R01.015.B04

FPP

FPP 1,10-trans cyclization

4.2.3.60;4.2.3.71; 4.2.3.9; 4.2.3.86; 4.2.3.76

18-20

R01.015.B05

FPP

FPP 1,10-trans cyclization

 4.2.3.22;4.2.3.23;4.2.3.60;4.2.3.71; 4.2.3.73; 4.2.3.72; 4.2.3.88; 4.2.3.100; 4.2.3.96; 4.2.3.75; 4.2.3.139

18-20

R01.015.B06

FPP

FPP 1,10-trans cyclization

4.2.3.60;4.2.3.71; 4.2.3.77;4.2.3.143

18-20

R01.015.C01

FPP

FPP 1,10-cis cyclization

4.2.3.13; 4.2.3.92; 4.2.3.129

21-24

R01.015.C02

FPP

FPP 1,10-cis cyclization

 

21-24

R01.015.C03

FPP

FPP 1,10-cis cyclization

4.2.3.125; 4.2.3.126; 4.2.3.91; 4.2.3.128; 4.2.3.127; 4.2.3.133

22, 23

R01.015.C04

FPP

FPP 1,10-cis cyclization

 

22, 23

R01.015.C05

FPP

FPP 1,10-cis cyclization

4.2.3.129

21-24

R01.015.C06

FPP

FPP 1,10-cis cyclization

4.2.3.98; 4.2.3.97; 4.2.3.63; 4.2.3.64

21-24

R01.015.C07

FPP

FPP 1,10-cis cyclization

 4.2.3.67

21-24

R01.015.C08

FPP

FPP 1,10-cis cyclization

4.2.3.62; 4.2.3.97

21-24

R01.015.D01

FPP

FPP 1,11-cis cyclization

4.2.3.80; 4.2.3.58

25

R01.015.D02

FPP

FPP 1,11-cis cyclization

4.2.3.57; 4.2.3.74; 4.2.3.136

26, 27

R01.015.E01

FPP

FPP 1,11-trans cyclization

4.2.3.104; 4.2.3.135; 4.2.3.7; 4.2.3.56

28-30

R01.015.E02

FPP

FPP 1,11-trans cyclization

4.2.3.104; 4.2.3.89

28-30

R01.015.E03

FPP

FPP 1,11-trans cyclization

4.2.3.104; 4.2.3.137

28-30

R01.020.F01

GGPP

GGPP 1,14 cyclization

4.2.3.8; 4.2.3.17

31, 32

R01.020.G01

GGPP

GGPP 1,11 + 10,14 cyclization

4.2.3.43

33

R01.020.H01

CPP

CPP 3,19 cyclization

4.2.3.44; 4.2.3.18; 4.2.3.32; 4.2.3.45; 4.2.3.131; 4.2.3.132

34-37

R01.020.H02

CPP

CPP 3,19 cyclization

4.2.3.18; 4.2.3.32; 4.2.3.131; 4.2.3.132

34-37

R01.020.H03

entCPP

entCPP 3,19 cyclization

4.2.3.30; 4.2.3.19; 4.2.3.103; 4.2.3.28; 4.2.3.31

34-37

R01.020.H04

entCPP

entCPP 3,19 cyclization

4.2.3.29

34-37

R01.020.H05

9a-CPP

9a-CPP 3,19 cyclization

4.2.3.34; 4.2.3.33

34-37

R01.020.H06

9a-CPP

9a-CPP 3,19 cyclization

4.2.3.35; 4.2.3.42

34-37

R01.005.N01

DMAPP

DMAPP isomerization

4.2.3.27

38

R02.030.A01

Oxido-squalene

Hopene like cyclization

5.4.99.38; 4.2.1.129;5.4.99.17; 4.2.1.123

39-41

R02.030.A02

Oxido-squalene

Lupeol, amyrin like cyclization

5.4.99.38; 4.2.1.125;5.4.99.37; 4.2.1.128;5.4.99.41; 5.4.99.34; 5.4.99.56; 5.4.99.51; 5.4.99.46;5.4.99.57; 5.4.99.34;5.4.99.55; 5.4.99.39;5.4.99.48;5.4.99.54;5.4.99.55; 5.4.99.35; 5.4.99.36; 5.4.99.49;5.4.99.50; 5.4.99.40;5.4.99.52

42, 43

R02.030.A03

Oxido-squalene

Lanosterol like cyclization

5.4.99.38; 5.4.99.32; 5.4.99.7;5.4.99.8;5.4.99.47; 5.4.99.33; 5.4.99.53

44, 45

R02.030.A04

Oxido-squalene

Arabidiol like cyclization

4.2.1.124; 5.4.99.31

46

R02.035.B01

C35 all-trans terpene

Sporulenol like cyclization

4.2.1.137

47, 48

R02.020.C01

GGPP

CPP

5.5.1.12; 5.5.1.16

36, 49, 50

R02.020.C02

GGPP

ent-CPP

5.5.1.13

36, 49, 50

R02.020.C03

GGPP

9a-CPP

5.5.1.14; 5.5.1.15

36, 49, 50

Table S1-1b. Mapping of EC to reaction channels

EC number

Common Name

Reaction Channel ID

4.2.3.6

trichodiene

R01.015.A01

4.2.3.7

pentalenene

R01.015.E01

4.2.3.8

casbene

R01.020.F01

4.2.3.9

aristolochene

R01.015.B04

4.2.3.10

(-)-endo-fenchol

R01.010.A01

4.2.3.11

sabinene hydrate

R01.010.A01

4.2.3.13

(+)-delta-cadinene

R01.015.C01

4.2.3.16

(S)-limonene

R01.010.A02

4.2.3.17

taxa-4,11-diene

R01.020.F01

4.2.3.18

abieta-7,13-diene

R01.020.H02; R01.020.H01

4.2.3.19

ent-kaurene

R01.020.H03

4.2.3.20

(R)-limonene

R01.010.A01

4.2.3.21

vetispiradiene

R01.015.B01

4.2.3.22

(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol

R01.015.B01; R01.015.B03; R01.015.B05

4.2.3.23

(+)-(R)-gemacrene A

R01.015.B01; R01.015.B03; R01.015.B05

4.2.3.24

amorpha-4,11-diene

R01.015.A05

4.2.3.27

isoprene

R01.005.N01

4.2.3.28

ent-cassa-12,15-diene

R01.020.H03

4.2.3.29

ent-sandaracopimara-8(14),15-diene

R01.020.H04

4.2.3.30

ent-pimara-8(14),15-diene

R01.020.H03

4.2.3.31

ent-pimara-9(11),15-diene

R01.020.H03

4.2.3.32

abieta-8(14),12-diene

R01.020.H02; R01.020.H01

4.2.3.33

stemar-13-ene

R01.020.H05

4.2.3.34

stemod-13(17)-ene

R01.020.H05

4.2.3.35

9beta-pimara-7,15-diene

R01.020.H06

4.2.3.37

(+)-epi-isozizaene

R01.015.A03

4.2.3.38

(E)-alpha-bisabolene

R01.015.A03; R01.015.A02; R01.015.A01; R01.015.A07; R01.015.A06; R01.015.A05; R01.015.A04; R01.015.A09; R01.015.A08; R01.015.A10

4.2.3.39

8-epi-cedrol

R01.015.A10

4.2.3.40

(Z)-gamma-bisabolene

R01.015.A03; R01.015.A02; R01.015.A01; R01.015.A07; R01.015.A06; R01.015.A05; R01.015.A04; R01.015.A09; R01.015.A08; R01.015.A10

4.2.3.42

aphidicolan-16beta-ol

R01.020.H06

4.2.3.43

fusicocca-2,10(14)-diene

R01.020.G01

4.2.3.44

isopimara-7,15-diene

R01.020.H01

4.2.3.45

phyllocladan-16alpha-ol

R01.020.H01

4.2.3.50

(+)-alpha-santalene

R01.015.A03

4.2.3.52

(4S)-beta-phellandrene

R01.010.A02

4.2.3.53

(+)-endo-beta-bergamotene

R01.015.A04

4.2.3.54

(-)-endo-alpha-bergamotene

R01.015.A04

4.2.3.55

(S)-beta-bisabolene

R01.015.A02; R01.015.A06; R01.015.A04; R01.015.A08; R01.015.A10

4.2.3.56

gamma-humulene

R01.015.E01

4.2.3.57

(-)-beta-caryophyllene

R01.015.D02

4.2.3.58

longifolene

R01.015.D01

4.2.3.59

(E)-gamma-bisabolene

R01.015.A03; R01.015.A02; R01.015.A01; R01.015.A07; R01.015.A06; R01.015.A05; R01.015.A04; R01.015.A09; R01.015.A08; R01.015.A10

4.2.3.60

germacrene C

R01.015.B01; R01.015.B02; R01.015.B03; R01.015.B04; R01.015.B05; R01.015.B06

4.2.3.61

(+)-5-epiaristolochene

R01.015.B01

4.2.3.62

(-)-gamma-cadinene

R01.015.C08

4.2.3.63

(+)-cubenene

R01.015.C06

4.2.3.64

(+)-epicubenol

R01.015.C06

4.2.3.65

zingiberene

R01.015.A06

4.2.3.66

beta-selinene

R01.015.B03

4.2.3.67

cis-muurola-3,5-diene

R01.015.C07

4.2.3.69

(+)-alpha-barbatene

R01.015.A02

4.2.3.70

patchoulol

R01.015.B03

4.2.3.71

(E,E)-germacrene B

R01.015.B01; R01.015.B02; R01.015.B03; R01.015.B04; R01.015.B05; R01.015.B06

4.2.3.72

(-)-alpha-gurjunene

R01.015.B05

4.2.3.73

(+)-valencene

R01.015.B05

4.2.3.74

presilphiperfolan-8beta-ol

R01.015.D02

4.2.3.75

(-)-germacrene D

R01.015.B05

4.2.3.76

(+)-delta-selinene

R01.015.B03; R01.015.B04

4.2.3.77

(+)-germacrene D

R01.015.B06

4.2.3.78

(+)-beta-chamigrene

R01.015.A02

4.2.3.79

(+)-thujopsene

R01.015.A02

4.2.3.80

alpha-longipinene

R01.015.D01

4.2.3.81

(-)-exo-alpha-bergamotene

R01.015.A02

4.2.3.82

(+)-alpha-santalene

R01.015.A02

4.2.3.83

(-)-beta-santalene

R01.015.A02

4.2.3.86

7-epi-alpha-selinene

R01.015.B04

4.2.3.87

alpha-guaiene

R01.015.B01

4.2.3.88

viridiflorene

R01.015.B05

4.2.3.89

(+)-beta-caryophyllene

R01.015.E02

4.2.3.90

5-epi-alpha-selinene

R01.015.B01

4.2.3.91

cubebol

R01.015.C03

4.2.3.92

(+)-gamma-cadinene

R01.015.C01

4.2.3.93

delta-guaiene

R01.015.B01

4.2.3.94

gamma-curcumene

R01.015.A03; R01.015.A05

4.2.3.95

(-)-alpha-cuprenene

R01.015.A01

4.2.3.96

avermitilol

R01.015.B05

4.2.3.97

(-)-delta-cadinene

R01.015.C06; R01.015.C08

4.2.3.98

(+)-T-muurolol

R01.015.C06

4.2.3.100

bicyclogermacrene

R01.015.B05

4.2.3.101

7-epi-sesquithujene

R01.015.A04

4.2.3.102

sesquithujene

R01.015.A03

4.2.3.103

ent-isokaurene

R01.020.H03

4.2.3.104

alpha-humulene

R01.015.E03; R01.015.E02; R01.015.E01

4.2.3.105

tricyclene

R01.010.A02

4.2.3.107

(+)-car-3-ene

R01.010.A02

4.2.3.108

1,8-cineole

R01.010.A01

4.2.3.109

(-)-sabinene

R01.010.A02; R01.010.A01

4.2.3.110

(+)-sabinene

R01.010.A02; R01.010.A01

4.2.3.111

(-)-alpha-terpineol

R01.010.A02

4.2.3.112

(+)-alpha-terpineol

R01.010.A01

4.2.3.113

terpinolene

R01.010.A02; R01.010.A01

4.2.3.114

gamma-terpinene

R01.010.A02; R01.010.A01

4.2.3.115

alpha-terpinene

R01.010.A02; R01.010.A01

4.2.3.116

(+)-camphene

R01.010.A01

4.2.3.117

(-)-camphene

R01.010.A02

4.2.3.118

2-methylisoborneol

R01.010.A01

4.2.3.119

(-)-alpha-pinene

R01.010.A02

4.2.3.120

(-)-beta-pinene

R01.010.A02

4.2.3.121

(+)-alpha-pinene

R01.010.A01

4.2.3.122

(+)-beta-pinene

R01.010.A01

4.2.3.123

beta-sesquiphellandrene

R01.015.A06

4.2.3.125

alpha-muurolene

R01.015.C03

4.2.3.126

gamma-muurolene

R01.015.C03

4.2.3.127

beta-copaene

R01.015.C03

4.2.3.128

beta-cubebene

R01.015.C03

4.2.3.129

(+)-sativene

R01.015.C05; R01.015.C01

4.2.3.131

miltiradiene

R01.020.H02; R01.020.H01

4.2.3.132

neoabietadiene

R01.020.H02; R01.020.H01

4.2.3.133

(-)-alpha-copaene

R01.015.C03

4.2.3.135

Delta6-protoilludene

R01.015.E01

4.2.3.136

(-)-alpha-isocomene

R01.015.D02

4.2.3.137

(E)-2-epi-beta-caryophyllene

R01.015.E03

4.2.3.138

(+)-epi-alpha-bisabolol

R01.015.A02; R01.015.A06; R01.015.A04; R01.015.A08; R01.015.A10

4.2.3.139

valerena-4,7(11)-diene

R01.015.B05

4.2.3.142

7-epizingiberene

R01.015.A06

4.2.3.143

kunzeaol

R01.015.B06

5.5.1.17

(S)-beta-macrocarpene

R01.015.A08

5.5.1.22

(–)-bornyl diphosphate

R01.010.A02

5.5.1.8

(+)-bornyl diphosphate

R01.010.A01

4.2.1.123

tetrahymanol

R02.030.A01

4.2.1.124

arabidiol

R02.030.A04

4.2.1.125

dammarenediol II

R02.030.A02

4.2.1.128

lupan-3beta,20-diol

R02.030.A02

4.2.1.129

hopanol

R02.030.A01

4.2.1.137

tetraprenyl-beta-curcumene

R02.035.B01

5.4.99.17

hop-22(29)-ene

R02.030.A01

5.4.99.31

thalianol

R02.030.A04

5.4.99.32

(17Z)-protosta-17(20),24-dien-3beta-ol

R02.030.A03

5.4.99.33

cucurbitadienol

R02.030.A03

5.4.99.34

germanicol

R02.030.A02

5.4.99.35

taraxerol

R02.030.A02

5.4.99.36

isomultiflorenol

R02.030.A02

5.4.99.37

dammara-20,24-diene

R02.030.A02

5.4.99.38

camelliol C

R02.030.A03; R02.030.A02; R02.030.A01

5.4.99.39

beta-amyrin

R02.030.A02

5.4.99.40

alpha-amyrin

R02.030.A02

5.4.99.41

lupeol

R02.030.A02

5.4.99.46

shionone

R02.030.A02

5.4.99.47

parkeol

R02.030.A03

5.4.99.48

achilleol B

R02.030.A02

5.4.99.49

glutinol

R02.030.A02

5.4.99.50

friedelin

R02.030.A02

5.4.99.51

baccharis oxide

R02.030.A02

5.4.99.52

alpha-seco-amyrin

R02.030.A02

5.4.99.53

marneral

R02.030.A03

5.4.99.54

beta-seco-amyrin

R02.030.A02

5.4.99.55

delta-amyrin

R02.030.A02

5.4.99.56

tirucalla-7,24-dien-3beta-ol

R02.030.A02

5.4.99.57

baruol

R02.030.A02

5.4.99.7

lanosterol

R02.030.A03

5.4.99.8

cycloartenol

R02.030.A03

5.5.1.12

(+)-copalyl diphosphate

R02.020.C01

5.5.1.13

ent-copalyl diphosphate

R02.020.C02

5.5.1.14

9alpha-copalyl diphosphate

R02.020.C03

5.5.1.15

terpentedienyl diphosphate

R02.020.C03

5.5.1.16

tuberculosinyl diphosphate

R02.020.C01


Reaction Channel Schemes:

Site-I reaction channels

R01.005.N01    (back to Channel List // back to EC List)

R01.010.A01    (back to Channel List // back to EC List)

R01.010.A02    (back to Channel List // back to EC List)

R01.011.A01    (back to Channel List // back to EC List)

R01.011.A02    (back to Channel List // back to EC List)

R01.015.A01    (back to Channel List // back to EC List)

R01.015.A02    (back to Channel List // back to EC List)

R01.015.A03    (back to Channel List // back to EC List)

R01.015.A04    (back to Channel List // back to EC List)

R01.015.A05    (back to Channel List // back to EC List)

R01.015.A06    (back to Channel List // back to EC List)

R01.015.A07    (back to Channel List // back to EC List)

R01.015.A08    (back to Channel List // back to EC List)

R01.015.A09    (back to Channel List // back to EC List)

R01.015.A10    (back to Channel List // back to EC List)

R01.015.B01    (back to Channel List // back to EC List)

R01.015.B02    (back to Channel List // back to EC List)

R01.015.B03    (back to Channel List // back to EC List)

R01.015.B04    (back to Channel List // back to EC List)

R01.015.B05    (back to Channel List // back to EC List)

R01.015.B06    (back to Channel List // back to EC List)

R01.015.C01    (back to Channel List // back to EC List)

R01.015.C02    (back to Channel List // back to EC List)

R01.015.C03    (back to Channel List // back to EC List)

R01.015.C04    (back to Channel List // back to EC List)

R01.015.C05    (back to Channel List // back to EC List)

R01.015.C06    (back to Channel List // back to EC List)

R01.015.C07    (back to Channel List // back to EC List)

R01.015.C08    (back to Channel List // back to EC List)

R01.015.D01    (back to Channel List // back to EC List)

R01.015.D02    (back to Channel List // back to EC List)

R01.015.E01    (back to Channel List // back to EC List)

R01.015.E02    (back to Channel List // back to EC List)

R01.015.E03    (back to Channel List // back to EC List)

R01.020.F01    (back to Channel List // back to EC List)

R01.020.G01    (back to Channel List // back to EC List)

R01.020.H01    (back to Channel List // back to EC List)

R01.020.H02    (back to Channel List // back to EC List)

R01.020.H03    (back to Channel List // back to EC List)

R01.020.H04    (back to Channel List // back to EC List)

R01.020.H05    (back to Channel List // back to EC List)

R01.020.H06    (back to Channel List // back to EC List)


Site-II reaction channels

R02.030.A01    (back to Channel List // back to EC List)

R02.030.A02    (back to Channel List // back to EC List)

 

R02.030.A03    (back to Channel List // back to EC List)

R02.030.A04    (back to Channel List // back to EC List)

R02.035.B01    (back to Channel List // back to EC List)

R02.020.C01    (back to Channel List // back to EC List)

R02.020.C02    (back to Channel List // back to EC List)

R02.020.C03    (back to Channel List // back to EC List)


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