Supplementary Datasets Supplementary Dataset 1. Results from … · Supplementary Datasets Supplementary Dataset 1. Results from retrobiosynthetic analysis of microbial modular natural

Supplementary Datasets

Supplementary Dataset 1. Results from retrobiosynthetic analysis of microbial

modular natural product antibacterials. A retrobiosynthetic algorithm was used to

cluster specific antibacterial natural products by their chemical scaffolds. Clustering

analysis yielded proposed classes based on conserved chemical scaffold, with the

number of structures in each class is listed along with a representative chemical structure

and statement on the mechanism of action or known cross resistance. Molecules which

are not present in this dataset were not accepted as inputs by our retrobiosynthetic

algorithm or were not specific antibacterial agents.

Proposed Class

(Members) Representative Structure

Mechanism of Action /

Target? *No known cross resistance

Aminoglycosides

1

(199)

Fortimicin C

Ribosome inhibitor1

Aminoglycosides

2

(42)

Kanamycin A

Ribosome inhibitor1

Cervimycins

(6)

Cervimycin

Unknown*2

Everninomicins

(81)

Everninomicin A

Ribosome inhibitor3

Nature Chemical Biology: doi:10.1038/nchembio.2018

Teicoplanins

(29)

Teicoplanin A

D-Ala-D-Ala chelator4

Sulfazecins

(8)

Sulfazecins

Penicillin binding

proteins5

Guadinomines

(4)

Guadinomine A

Type 3 Secretion system6

Penicillins

(19)

Penicillin G

Penicillin binding

proteins5

Dapdiamides

(2)

Dapdiamide E

Glucosamine-6-

phosphate synthase7


Parvodicins

(31)

Parvodicin A


Vancomycins

(34)

Vancomycin


Ngercheumicins

(4)

Ngercheumicin A

Unknown


Nocathiacins

(4)

Nocathiacin I

Ribosome inhibitor8

SF-1902s

(3)

SF-1902

Type 1 signal peptidase9

Pyloricidins

(4)

Pyloricidin A

Unknown*10

Cyclothialidines

(5)

Cyclothialidine A

DNA gyrase11


Glysperins

(5)

Glysperin A

Unknown*12

Mycoplanecins

(4)

Mycoplanecin A

Unknown*13

Feglymycins

(2)

Feglymycin

UDP-N-

acetylglucosamine-3-

enolpyruvyltransferase14

Salinamides

(6)

Salinamide A

RNA polymerase15

Viridogriseins

(14)

Neoviridogrisein I

Ribosome inhibitor1


Virginiamycins

(21)

Virginiamycin-S2

Ribosome inhibitor1

Tumescenamides

(2)

Tumescenamide A

Unknown

Peptidolipins

(5)

Peptidolipin C

Unknown

Berninamycins

(3)

Berninamycin B

Ribosome inhibitor8

Sulfomycins

(21)

Sulfomycin I

Ribosome inhibitor8


Champacyclins

(1)

Champacyclin

Unknown

Radamycins

(2)

Radamycin A

Ribosome inhibitor8

Tripropeptins

(10)

Tripropeptin A

Undecaprenyl phosphate

binder16

Telomycins

(3)

Telomycin

Previously unknown

Cardiolipin binder

Griselimycins

(3)

Unknown*13


Griselimycin A

Depsichlorins

(1)

Depsichlorin

Unknown

Cycloheptamycins

(1)

Cycloheptamycin

Unknown

Tridecaptins

(8)

Tridecaptin A

Unknown*17

(Outer membrane)

Octapeptins

(9)

Octapeptin A2

LPS-binder18

Polymyxins

(20)

Polymyxin A

LPS-binder19


Polypeptins

(6)

Polypeptin B

Unknown

Friulimicins

(23)

Friulimicin A

Undecaprenyl phosphate

binder20

Calcium-

dependent

antibiotics

(21)

Daptomycin

Membrane disruption21

Teixobactins

(1)

Teixobactin

Lipid II binder22


Katanosins

(4)

Katanosin A

Peptidoglycan

transglycosylase23

Imacidins

(6)

Imacidin A

Unknown*24

(Cell wall)

Thiopeptins

(7)

Thiopeptin A1

Ribosome inhibitor8

WAP-8294

(6)

WAP-8294A

Unknown


Lysocins

(7)

Lysocin E

Menaquinone binder25

Kawaguchipeptins

(2)

Kawaguchipeptin A

Unknown

Cerexins

(9)

Cerexin A

Unknown

Tyrocidines

(12)

Tyrocidine A1


Bacitracins

(15)

Bacitracin A

Undecaprenyl binder27


Gramicidins

(5) Gramicidin C1


Mureidomycins

(7)

Mureidomycin A

Peptidoglycan

translocase29

Cyclomarins

(4)

Ilamycin A

ClpP protease30

Bottromycins

(6)

Bottromycin D

Ribosome inhibitor31

Longicatenamycin

(1)

Longicatenamycin A

Unknown


Galantins

(2)

Galantin I

Unknown

Pargamicins

(4)

Pargamicin A

Unknown*32

(Membrane)

Siomycins

(9)

Siomycin A

Ribosome inhibitor8

Mannopeptimycins

(10)

Mannopeptimycin alpha

Lipid II Binder33


Acyl

depsipeptides

(7)

A-54556A

ClpP protease34

Tauramamides

(1)

Tauramamide

Unknown

Lydiamycins

(4)

Lydiamycin A

Unknown

Janthinomycins

(2)

Janthinomycin A

Unknown*35

(Cell wall)

GE 23077s

(2)

GE 23077

RNA polymerase36


Pheganomycins

(6)

Pheganomycin D

Unknown*37

(Mycobacterial cell wall

or membrane)

Surfactins

(3)

Surfactin C1


Capreomycins

(2)

Capreomycin II A

Ribosome inhibitor1

Xenematides

(4)

Xenematide A

Unknown


Plantazolicins

(2)

Plantazolicin A

Unknown

Thiocillins

(8)

Thiocillin I

Ribosome inhibitor8

Thiazomycins

(17)

Thiazomycin A

Ribosome inhibitor8

Viomycins

(8)

Ribosome inhibitor1

Albomycins

(5)

Albomycin A1

Serine tRNA-synthetase39


SQ 28546s

(3)

SQ 28546

Unknown

GE 2270s

(11)

GE 2270 C2B

Elongation factor Tu40

Arylomycins

(12)

Arylomycin A1


PB-5266s

(9)

PB-5266

Penicillin-binding

proteins5

Calpinactam

(1)

Calpinactam

Unknown

Argyrins

(2)

A-21459 A

Elongation factor G42


Edeines

(4)

Edeine B1

Ribosome inhibitor1

Monamycins

(13)

Monamycin A

Unknown*43

(Membrane)

Cystobactamids

(3)

Cystobactamid 919-2

DNA gyrase44

Lavendomycins

(1)

Lavendomycin

Unknown

Antrimycins

(7)

Antrimycin

Unknown


Serratiomycins

(2)

Serratiomycin

Unknown

Globomycins

(7)

Globomycin


Argimicins

(3)

Argimicin C

Unknown*45

(Photosynthesis)

Unnarmicins

(3)

Unnarmicin C

Unknown

Pacidamycins

(20)

Pacidamycin 1

Peptidoglycan

translocase29


Cephalosporins

(138)

Cephalosporin C

Penicillin-binding

proteins5

Cepacins

(4)

Cepacin A

Unknown

Corallopyronins

(3)

Corallopyronin A

RNA polymerase46

Isariotins

(5)

Isariotin A

Unknown

Paulomycins

(14)

Paulomycin A


Lankacidins

(8)

Lankacidin S


Andrimids

(4)

Andrimid

Acetyl-CoA

carboxylase49


Streptolydigins

(6)

Streptolydigin

RNA polymerase36

Ansamycins

(26)

Rifamycin G

RNA polymerase36

Erythromycins &

mycinamycins

(134)

Erythromycin F

Ribosome inhibitor1

Tylosins

(184)

Tylosin A

Ribosome inhibitor1

Pannomycins

(1)

Pannomycin

SecA ATPase50


Elansolids

(4)

Elansolid A2

Unknown

Aerocyanidins

(3)

Aerocyanidin

Unknown

Fidaxomicins

(8)

Fidaxomicin

RNA polymerase36

Lipomycins

(2)

Lipomycin A


Cineromycins

(6)

Cineromycin B

Unknown

Nargenicins

(11)

Nargenicin C1

DNA polymerase52

Resorcinomycins

(3)

Resorcinomycin A

Unknown


Aminocoumarins

(10)

Novobiocin

DNA gyrase53

Sperabillins

(3) Sperabillin A

Unknown*54

(Membrane)

Thuggacins

(4)

Thuggacin A

NADPH oxidase55

Lincosamides

(16)

Lincomycin A

Ribosome inhibitor1

Thiolactomycin

(3)

Thiolactomycin-2

FabB / F56

Myxopyronins

(5)

Myxopyronin A

RNA polymerase36

Simocyclinones

(2)

Simocyclinone D4

DNA gyrase57

Bactobolins

(4)

Bactobolin F



Pyridomycins

(2)

Pyridomycin

FabI / InhA59

Muraymycins

(21)

Muraymycin A1

Peptidoglycan

translocase60

Chloroorienticins

(9)

Chloroorienticin C


Ramoplanins

(12)

Ramoplanin A1

Lipid II binder61

Bogorols

(9)

Bogorol A

Unknown


Izumenolide

(1)

Izumenolide

Beta-lactamase

inhibitor62

Sorangicins

(14)

Sorangicin A1

RNA polymerase63

Etnangien

(1)

Etnangien

RNA polymerase64

Kanchanamycin

(4)

Kanchanamycin A

Unknown

Tubelactomicin

(5)

Tubelactomicin A

Unknown65

(Ribosome)

Maduralide

(1)

Maduralide

Unknown


Anthracimycin

(1)

Anthracimycin

Unknown*66

(DNA / RNA synthesis)

Halstoctasanolids

(3)

Halstoctasanolid B

Unknown

YM-32890

(1)

YM-32890

Unknown

Macrolactins

(18)

Macrolactin R

Peptide deformylase, 67

FabG68

Difficidins

(3)

Difficidin


Ripostatins

(2)

Ripostatin A

RNA polymerase70


Elfamycins

(22)

Phenelfamycin A


Kirromycins

(15)

Kirromycin


Chaxalactins

(3)

Chaxalactin A

Unknown

Enacyloxins

(2)

Enacyloxin IA


Stenothricins

(4)

Stenothricin I

Unknown*74

(Cell wall)

Fasamycins

(2)

Fasamycin A

FabB / F75

CJ-13100s

(5)

CJ-13102

Unknown


Myxovirescins

(29)

Myxovirescin A2


Sorangiolide

(3)

Sorangiolide A

Unknown77

(Membrane)

Mupirocins and

Thiomarinols

(16) Mupirocin B

Ile-tRNA synthetase78

Angiolams

(4)

Angiolam A


Bacillaenes

(3) Bacillaene

Unknown80

(Protein synthesis)

Korormicins

(6)

Korormicin

Na-dependent NADH-

quinone reductase81

Kalimantacins

(6) Kalimantacin A

FabI82

Nitracidomycins

(4)

Nitracidomycin A

Unknown

Obafluorins

(2)

Obafluorin

Unknown


Amiclenomycins

(5)

Amiclenomycin

Biotin aminotransferase83

Neocitreamicins

(2)

Neocitreamicin I

Unknown84

(Membrane)

A-500359s

(2)

A-500359 A

Peptidoglycan

translocase85

Pantocin A

(1)

Pantocin A

L-histidinol phosphate

aminotransferase86

Nourseimycins

(1)

Nourseimycin

Unknown87

(Amino acid metabolism)

Aporpinones

(5)

Aporpinone A

Unknown

Quercinic acids

(3)

Didehydrocarboxyacetylquercinic acid

Unknown


Aszonapyrones

(3)

Aszonapyrone A

Unknown

Luminamycins

(3)

Luminamicin

Unknown

Fusidic acids

(20)

Fusidic acid

Elongation factor G88

Kibdelomycins

(3)

Kibdelomycin

DNA gyrase89

Biphenomycins

(4)

Biphenomycin A


Butirosins

(17)

Butirosin A

Ribosome inhibitor1


Clavamycins

(4)

Clavamycin A

Penicillin-binding

proteins5

OA-6129s

(18)

OA-6129A

Penicillin-binding

proteins5

Madumicins

(15)

Madumicin II

Ribosome inhibitors1

Moenomycins

(15)

Moenomycin A

Peptidoglycan

transglycosylase91

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Supplementary Datasets Supplementary Dataset 1. Results from … · Supplementary Datasets Supplementary Dataset 1. Results from retrobiosynthetic analysis of microbial modular natural