Polyketide (ポリケチド)
Class Overview
Polyketides are synthesized through the polymerization of acetyl units (β-ketomethylene chain).
Table 1. Polyketide Classification
1st Class
|
PK4: Four C2 Units
orsellinic acid, 6-methylsalicylic acid, triacetic acid lactone, asperlin, usnic acid, methylphloracetophenone, penicillic acid, patulin
|
PK5: Five C2 Units
citrinin, aflatoxin, augenone, sepedonin, stipitatonic acid
|
PK6: Six C2 Units
plumbagin, 7-methyljuglone, juglone, variotin
|
PK7: Seven and eight C2 Units
Anthraquinone rings
griseofulvin, rubrofusarin, emodin, alizarin, pachybasin, xanthone, versicolorin A, aflatoxin B1, sterigmatocystin, tajixanthone
|
PK9: Nine C2 Units
Tetracyclines
terramycin, aureomycin, daunomycin
|
|
Polyketide Synthase (PKS)
species |
Actinomycetes |
Cyanobacteria |
γ-Proteobacteria |
Fungi |
Dinoflagellates
|
Type-I PKS
|
Ο |
Ο |
Ο |
Χ |
Ο
|
Type-II PKS
|
Ο |
Χ |
Χ |
Ο |
Χ
|
NRPS
|
Ο |
Ο |
Ο |
Ο |
Χ
|
deoxysugar
|
Ο |
Χ |
Χ |
Χ |
Χ
|
Terpene
|
Δ |
Χ |
Χ |
Ο |
Χ
|
Type I PKS (non-iterative)
- Multi catalytic domains exist in a single protein
- Chain length is determined by the number of catalytic domains.
- Products are non-aromatic and have larger masses.
Ref. Erythromycin biosynthesis in Nat Prod Rep 18, 380 (2001)
Type II PKS (iterative)
- Three proteins (KSα, KSβ, ACP) are repeatedly used for carbon chain elongation.
- Chain length is determined by another protein, CLF.
- In bacteria, products are aromatic (e.g. chiorotetracycline, pradimicin).
- In fungi, products are both non-aromatic and aromatic.
Non-ribosomal peptide synthase (NRPS)
Coupling with PKS and NRPS
- vancomycin ()
- leinamycin (Curr opin chem biol 7:285, 2003)
- pseurotin (chem bio chem 8:1736-1743, 2007)
- curacin (curr opin chem biol 13:216, 2009)
- epothilone
- rapamycin
PKS in Fungi
- both aromatic and non-aromatic compounds are generated by iterative PKS
- methyl branch is transferred from methionine, not methylmalonyl CoA
Ref. Dewick, PM Medicinal Natural Products (2009)
Decoration
deoxysugars
deoxygenation, c-methylation, amination, n-methylation, ketosugar,
Unusual structures
Phoma
|
zaragozic acid, phomoidoride
|
Streptomyces
|
yatakemycin, leinamycin, saframycin, neocarzinostatin, staurosporin, FR182877
|
Other bacteria
|
PKS-NRPS hybrid type
Curacin A (Lyngbya), Shiphonazole (Herpetosiphon), Jamaicamide A (Lyngbya), Cylindrospermopsin (Cylindrospermopsis)
|
1,3,8-Trihydroxyaceto-Naphthalene
|
|
1,3-Dihydroxy-N-Methylacridone
|
|
3,8-Dihydroxy-1-Methylanthraquinone-2-Carboxylic_Acid
|
|
4-Hydroxy-2-Quinolone
|
|
5,7-Dihydroxy-2-Methylchromone
|
|
5-Methylorsellinic_Acid
|
|
6-Deoxy-Erythronolide_B
|
|
6-Methoxymellein
|
|
6-Methyl_Salicylic_Acid
|
|
Actinorhodin
|
|
Adhyperforin
|
|
Aflatoxin_B1
|
|
Aflatoxin_B2
|
|
Aflatoxin_G1
|
|
Aflatoxin_G2
|
|
Aflatoxin_M1
|
|
Aloe-Emodin
|
|
Aloesaponarin_II
|
|
Alternapyrone
|
|
Alternaric_Acid
|
|
Alternariol
|
|
Amphotericin_B
|
|
Andrimid_
|
|
Ascomycin
|
|
Aslaniol
|
|
Aslanipyrone
|
|
Asperlactone
|
|
Asperlin
|
|
Aspyridone_A
|
|
Aspyridone_B
|
|
Aspyrone
|
|
Asteltoxin
|
|
Astepyrone
|
|
Atrochrysone
|
|
Atrochrysone_Carboxylic_Acid
|
|
Aureothin
|
|
Austdiol
|
|
Avenaciolide
|
|
Averantin
|
|
Avermectin_B1A
|
|
Avermectin_B2A
|
|
Averufin
|
|
Avilamycin
|
|
Barnol
|
|
Benzophenone
|
|
Bikaverin
|
|
Botryodiplodin
|
|
Brefeldin_A
|
|
Brevetoxin_A
|
|
Brevetoxin_B
|
|
C-1027
|
|
Calichemicin_Gamma1
|
|
Cannabidiol
|
|
Cannabigerolic_Acid
|
|
Cannabinol
|
|
Cercosporin
|
|
Chlortetracycline
|
|
Chrysomycin_A
|
|
Chrysomycin_B
|
|
Chrysophanol
|
|
Chrysophanol_Anthrone
|
|
Ciguatoxin_I
|
|
Citreomontanin
|
|
Citreoviridin
|
|
Citrinin
|
|
Clavatol
|
|
Coarctatin
|
|
Colletodiol
|
|
Compactin
|
|
Curvularin
|
|
Deoxyherquienone
|
|
Deoxyradicin
|
|
Dihydroisocoumarin
|
|
Diplosporin
|
|
Discodermolide
|
|
Doramectin
|
|
Dothistromin
|
|
Doxorubicin
|
|
Emodin
|
|
Emodin_Anthrone
|
|
Emodin_Dianthrone
|
|
Endocrocin
|
|
Endocrocin_Anthrone
|
|
Enniatin_B
|
|
Enterocin
|
|
Epothilone_A
|
|
Epothilone_B
|
|
Epothilone_C
|
|
Epothilone_D
|
|
Epoxydon
|
|
Epsilon-Pyrromycinone
|
|
Erythromycin
|
|
Flavipin
|
|
Fumigatin
|
|
Fumonisin_B1
|
|
Furanomycin
|
|
Geldanamycin
|
|
Griseofulvin
|
|
Griseophenone_B
|
|
Griseophenone_C
|
|
Humulone
|
|
Hyperforin
|
|
Hypericin
|
|
Islandicin
|
|
Isoepoxydon
|
|
Isousnic_Acid
|
|
Ivermectin
|
|
Khellin
|
|
Lasalocid
|
|
Lecanoric_Acid
|
|
Leucomycin_A1
|
|
Ll-D253Alpha
|
|
Lovastatin
|
|
M-Cresol
|
|
Melanin
|
|
Mellein
|
|
Methylphloracetophenone
|
|
Mollisin
|
|
Monensin_A
|
|
Multicolic_Acid
|
|
Mycolactone
|
|
Mycophenolic_Acid
|
|
Myxalamide
|
|
Myxothiazol_Z
|
|
Niddamycin
|
|
Norsolorinic_Acid
|
|
Nystatin
|
|
Ochratoxin_A
|
|
Ochrephilone
|
|
Okadaic_Acid
|
|
Oleandomycin
|
|
Olivetolic_Acid
|
|
O-Methylasparvenone
|
|
Orcinol
|
|
Orsellinic_Acid
|
|
Oxytetracycline
|
|
Palitantin
|
|
Patulin
|
|
Penicillic_Acid
|
|
Phloracetophenone
|
|
Phlorisobutyrophenone
|
|
Phlorisovalerophenone
|
|
Physcion
|
|
Picromycin
|
|
Pimaricin
|
|
Pretetramide
|
|
Protohypericin
|
|
Pyochelin
|
|
Pyoluteorin
|
|
Radicin
|
|
Rapamycin
|
|
Ravenilin
|
|
Rhein
|
|
Rifabutin
|
|
Rifamycin_B
|
|
Rifapentine
|
|
Rosellisin
|
|
Rubrofusarin
|
|
Rubropunctatin
|
|
Sclerin
|
|
Sclerotinin_A
|
|
Sek4
|
|
Sek4B
|
|
Selamectin
|
|
Sennidin_A
|
|
Sennidin_B
|
|
Sennidin_C
|
|
Sennidin_D
|
|
Sennosides_A
|
|
Sennosides_B
|
|
Sennosides_C
|
|
Sennosides_D
|
|
Sepedonin
|
|
Siccanin
|
|
Silvaticamide
|
|
Sma76A
|
|
Sma76B
|
|
Sma76C
|
|
Soraphen_A
|
|
Spinulosin
|
|
Spiramycin_I
|
|
Sterigmatocystin
|
|
Stigmatellin_A
|
|
Stipitatonic_Acid
|
|
Sulochrin
|
|
Tacrolimus
|
|
Tajixanthone
|
|
Tennellin
|
|
Terrein
|
|
Terrequinone_A
|
|
Tetracenomycin_F2
|
|
Tetracycline
|
|
Tetrahydro_Cannabinol
|
|
Tetrahydroxynaphthalene
|
|
Triacetic_Acid_Lactone
|
|
T-Toxin
|
|
Tylactone
|
|
Tylosin
|
|
Urushiol_III
|
|
Usnic_Acid
|
|
Variotin
|
|
Versicolorin_A
|
|
Versicolorin_B
|
|
Versiconal
|
|
Versiconal_Acetate
|
|
Visnagin
|
|
Wa-Naphthopyron
|
|
Zaragozic_Acids_A
|
|
Zearalenone
|
|
Subcategories
This category has only the following subcategory.