Entry |
|
Name |
Biosynthesis of 12-, 14- and 16-membered macrolides |
Including |
Tylosin biosynthesis, Mycinamicin biosynthesis, Erythromycin biosynthesis, Oleandomycin biosynthesis, Pikromycin/methymycin biosynthesis, Avermectin biosynthesis |
Class |
Metabolism; Metabolism of terpenoids and polyketides
|
Pathway map |
rn00522 | Biosynthesis of 12-, 14- and 16-membered macrolides |

|
Module |
M00773 | Tylosin biosynthesis, methylmalonyl-CoA + malonyl-CoA => tylactone => tylosin [PATH:rn00522] |
M00774 | Erythromycin biosynthesis, propanoyl-CoA + methylmalonyl-CoA => deoxyerythronolide B => erythromycin A/B [PATH:rn00522] |
M00775 | Oleandomycin biosynthesis, malonyl-CoA + methylmalonyl-CoA => 8,8a-deoxyoleandolide => oleandomycin [PATH:rn00522] |
M00776 | Pikromycin/methymycin biosynthesis, methylmalonyl-CoA + malonyl-CoA => narbonolide/10-deoxymethynolide => pikromycin/methymycin [PATH:rn00522] |
M00777 | Avermectin biosynthesis, 2-methylbutanoyl-CoA/isobutyryl-CoA => 6,8a-Seco-6,8a-deoxy-5-oxoavermectin 1a/1b aglycone => avermectin A1a/B1a/A1b/B1b [PATH:rn00522] |
M00934 | Mycinamicin biosynthesis, malonyl-CoA + methylmalonyl-CoA => protomycinolide IV => mycinamicin II [PATH:rn00522] |
|
Drug |
D00140 | Erythromycin (JP18/USP/INN) |
D03098 | Berythromycin (USAN/INN) |
|
Reaction |
R00918 | propanoyl-CoA:(2S)-methylmalonyl-CoA malonyltransferase (cyclizing); propanoyl-CoA:(2S)-methylmalonyl-CoA 2-C-acyltransferase (decarboxylating, oxoacyl-reducing and cyclizing) |
R02858 | S-adenosyl-L-methionine:macrocin 3'''-O-methyltransferase |
R02859 | S-adenosyl-L-methionine:demethylmacrocin 2'''-O-methyltransferase |
R05270 | 6-deoxyerythronolide-B,reduced ferredoxin:oxygen oxidoreductase |
R05520 | S-adenosyl-L-methionine:erythromycin-C 3''-O-methyltransferase |
R05521 | erythromycin-B,NADPH:oxygen oxidoreductase (12-hydroxylating) |
R05522 | erythromycin-D,NADPH:oxygen oxidoreductase (12-hydroxylating) |
R05530 | dTDP-L-mycarose:erythronolide-B 3-O-alpha-mycarosyltransferase |
R05531 | dTDP-D-desosamine:3-O-mycarosylerythronolide-B 5-O-beta-D-desosaminyltransferase |
R05532 | S-adenosyl-L-methionine:erythromycin-D 3''-O-methyltransferase |
R06450 | dTDP-alpha-D-mycaminose:tylactone 5-O-beta-D-mycaminosyltransferase |
R06451 | dTDP-6-deoxy-alpha-D-allose:5-O-beta-D-mycaminosyltylonolide 23-O-6-deoxy-beta-D-allosyltransferase |
R06452 | dTDP-L-mycarose:demethyllactenocin 4'-O-alpha-mycarosyltransferase |
R06456 | S-adenosyl-L-methionine:L-olivosyl-oleandolide B 3-O-methyltransferase |
R06458 | (2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (10-deoxymethynolide forming) |
R06459 | (2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (narbonolide forming) |
R06460 | dTDP-3-dimethylamino-3,4,6-trideoxy-alpha-D-glucopyranose:10-deoxymethynolide 3-dimethylamino-4,6-dideoxy-alpha-D-glucosyltransferase |
R06461 | dTDP-3-dimethylamino-3,4,6-trideoxy-alpha-D-glucopyranose:narbonolide 3-dimethylamino-4,6-dideoxy-alpha-D-glucosyltransferase |
R06462 | 10-deoxymethymycin,reduced ferredoxin:oxygen oxidoreductase (neomethymycin-forming) |
R06463 | 10-deoxymethymycin,reduced ferredoxin:oxygen oxidoreductase (methymycin-forming) |
R06464 | narbomycin,reduced ferredoxin:oxygen oxidoreductase (pikromycin-forming) |
R09822 | S-adenosyl-L-methionine:mycinamicin VI 2''-O-methyltransferase |
R09823 | S-adenosyl-L-methionine:mycinamicin III 3''-O-methyltransferase |
R10626 | narbomycin,reduced ferredoxin:oxygen oxidoreductase (neopikromycin-forming) |
R10627 | narbomycin,reduced ferredoxin:oxygen oxidoreductase (novapikromyin-forming) |
R10628 | 10-deoxymethymycin,reduced ferredoxin:oxygen oxidoreductase (novamethymycin-forming) |
R10656 | 20-oxo-5-O-beta-mycaminosyltylactone,reduced ferredoxin:oxygen oxidoreductase (23-hydroxylating) |
R10874 | dTDP-6-deoxy-alpha-D-allose:mycinamicin-VII 21-O-6-deoxy-beta-D-allosyltransferase |
R10875 | mycinamicin-VIII,NADPH:oxygen oxidoreductase (21-hydroxylating) |
R10876 | dTDP-3-dimethylamino-3,4,6-trideoxy-alpha-D-glucopyranose:protomycinolide-IV 5-O-(3-dimethylamino-3,4,6-trideoxy-beta-D-glucosyl)transferase; dTDP-D-desosamine:protomycinolide-IV 5-O-beta-D-desosaminyltransferase |
R10877 | mycinamicin-IV,NADPH:oxygen oxidoreductase (14-hydroxylating) |
R10878 | mycinamicin-V,NADPH:oxygen oxidoreductase (12,13-epoxidizing) |
|
Compound |
C06630 | 3-O-alpha-Mycarosylerythronolide B |
C11953 | 6,8a-Seco-6,8a-deoxy-5-oxoavermectin ''2b'' aglycone |
C11954 | 5-Oxoavermectin ''2b'' aglycone |
C11955 | Avermectin B2b aglycone |
C11956 | Avermectin A2b aglycone |
C11957 | Avermectin B2b monosaccharide |
C11958 | Avermectin A2b monosaccharide |
C11961 | 6,8a-Seco-6,8a-deoxy-5-oxoavermectin ''1b'' aglycone |
C11962 | 5-Oxoavermectin ''1b'' aglycone |
C11963 | Avermectin B1b aglycone |
C11964 | Avermectin A1b aglycone |
C11965 | Avermectin B1b monosaccharide |
C11966 | Avermectin A1b monosaccharide |
C11969 | 6,8a-Seco-6,8a-deoxy-5-oxoavermectin ''2a'' aglycone |
C11970 | 5-Oxoavermectin ''2a'' aglycone |
C11971 | Avermectin B2a aglycone |
C11972 | Avermectin A2a aglycone |
C11973 | Avermectin B2a monosaccharide |
C11974 | Avermectin A2a monosaccharide |
C11977 | 6,8a-Seco-6,8a-deoxy-5-oxoavermectin ''1a'' aglycone |
C11978 | 5-Oxoavermectin ''1a'' aglycone |
C11979 | Avermectin B1a aglycone |
C11980 | Avermectin A1a aglycone |
C11981 | Avermectin B1a monosaccharide |
C11982 | Avermectin A1a monosaccharide |
C11992 | L-Oleandrosyl-oleandolide |
C12001 | 5-O-beta-D-Mycaminosyltylactone |
C12002 | 5-O-beta-D-Mycaminosyltylonolide |
C20760 | 20-Oxo-5-O-beta-mycaminosyltylactone |
|
Reference |
|
Authors |
Hertweck C |
Title |
The biosynthetic logic of polyketide diversity. |
Journal |
|
Reference |
|
Authors |
Long PF, Wilkinson CJ, Bisang CP, Cortes J, Dunster N, Oliynyk M, McCormick E, McArthur H, Mendez C, Salas JA, Staunton J, Leadlay PF |
Title |
Engineering specificity of starter unit selection by the erythromycin-producing polyketide synthase. |
Journal |
|
Reference |
|
Authors |
Bisang C, Long PF, Cortes J, Westcott J, Crosby J, Matharu AL, Cox RJ, Simpson TJ, Staunton J, Leadlay PF |
Title |
A chain initiation factor common to both modular and aromatic polyketide synthases. |
Journal |
|
Reference |
|
Authors |
Katz L |
Title |
The DEBS paradigm for type I modular polyketide synthases and beyond. |
Journal |
|
Reference |
|
Authors |
Kittendorf JD, Beck BJ, Buchholz TJ, Seufert W, Sherman DH |
Title |
Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase. |
Journal |
|
Reference |
|
Authors |
Beck BJ, Yoon YJ, Reynolds KA, Sherman DH |
Title |
The hidden steps of domain skipping: macrolactone ring size determination in the pikromycin modular polyketide synthase. |
Journal |
|
Reference |
|
Authors |
Chen S, Roberts JB, Xue Y, Sherman DH, Reynolds KA |
Title |
The Streptomyces venezuelae pikAV gene contains a transcription unit essential for expression of enzymes involved in glycosylation of narbonolide and 10-deoxymethynolide. |
Journal |
|
Reference |
|
Authors |
Kim BS, Cropp TA, Beck BJ, Sherman DH, Reynolds KA |
Title |
Biochemical evidence for an editing role of thioesterase II in the biosynthesis of the polyketide pikromycin. |
Journal |
|
Reference |
|
Authors |
Ikeda H, Omura S |
Title |
Avermectin Biosynthesis. |
Journal |
|
Reference |
|
Authors |
Ikeda H, Nonomiya T, Omura S |
Title |
Organization of biosynthetic gene cluster for avermectin in Streptomyces avermitilis: analysis of enzymatic domains in four polyketide synthases. |
Journal |
|
Reference |
|
Authors |
Volchegursky Y, Hu Z, Katz L, McDaniel R |
Title |
Biosynthesis of the anti-parasitic agent megalomicin: transformation of erythromycin to megalomicin in Saccharopolyspora erythraea. |
Journal |
|
Reference |
|
Authors |
Peiru S, Menzella HG, Rodriguez E, Carney J, Gramajo H |
Title |
Production of the potent antibacterial polyketide erythromycin C in Escherichia coli. |
Journal |
|
Reference |
|
Authors |
Useglio M, Peiru S, Rodriguez E, Labadie GR, Carney JR, Gramajo H |
Title |
TDP-L-megosamine biosynthesis pathway elucidation and megalomicin a production in Escherichia coli. |
Journal |
|
Reference |
|
Authors |
Tsai SC, Miercke LJ, Krucinski J, Gokhale R, Chen JC, Foster PG, Cane DE, Khosla C, Stroud RM |
Title |
Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: versatility from a unique substrate channel. |
Journal |
|
Reference |
|
Authors |
Savino C, Montemiglio LC, Sciara G, Miele AE, Kendrew SG, Jemth P, Gianni S, Vallone B |
Title |
Investigating the structural plasticity of a cytochrome P450: three-dimensional structures of P450 EryK and binding to its physiological substrate. |
Journal |
|
Reference |
|
Authors |
Hsieh YJ, Kolattukudy PE. |
Title |
Inhibition of erythromycin synthesis by disruption of malonyl-coenzyme A decarboxylase gene eryM in Saccharopolyspora erythraea. |
Journal |
|
Reference |
|
Authors |
Donadio S, Staver MJ, Katz L. |
Title |
Erythromycin production in Saccharopolyspora erythraea does not require a functional propionyl-CoA carboxylase. |
Journal |
|
Reference |
|
Authors |
Summers RG, Donadio S, Staver MJ, Wendt-Pienkowski E, Hutchinson CR, Katz L. |
Title |
Sequencing and mutagenesis of genes from the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea that are involved in L-mycarose and D-desosamine production. |
Journal |
|
Reference |
|
Authors |
Rawlings BJ. |
Title |
Type I polyketide biosynthesis in bacteria (part B). |
Journal |
|
Reference |
|
Authors |
Rawlings BJ. |
Title |
Type I polyketide biosynthesis in bacteria (Part A--erythromycin biosynthesis). |
Journal |
|
Reference |
|
Authors |
Borisova SA, Liu HW |
Title |
Characterization of glycosyltransferase DesVII and its auxiliary partner protein DesVIII in the methymycin/picromycin biosynthetic pathway. |
Journal |
|
Reference |
|
Authors |
Hong JS, Park SJ, Parajuli N, Park SR, Koh HS, Jung WS, Choi CY, Yoon YJ |
Title |
Functional analysis of desVIII homologues involved in glycosylation of macrolide antibiotics by interspecies complementation. |
Journal |
|
Reference |
|
Authors |
Rodriguez E, Peiru S, Carney JR, Gramajo H |
Title |
In vivo characterization of the dTDP-D-desosamine pathway of the megalomicin gene cluster from Micromonospora megalomicea. |
Journal |
|
Reference |
|
Authors |
Moncrieffe MC, Fernandez MJ, Spiteller D, Matsumura H, Gay NJ, Luisi BF, Leadlay PF |
Title |
Structure of the glycosyltransferase EryCIII in complex with its activating P450 homologue EryCII. |
Journal |
|
Reference |
|
Authors |
Yuan Y, Chung HS, Leimkuhler C, Walsh CT, Kahne D, Walker S |
Title |
In vitro reconstitution of EryCIII activity for the preparation of unnatural macrolides. |
Journal |
|
Reference |
|
Authors |
Sherman DH, Li S, Yermalitskaya LV, Kim Y, Smith JA, Waterman MR, Podust LM |
Title |
The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae. |
Journal |
|
Reference |
|
Authors |
Li S, Ouellet H, Sherman DH, Podust LM |
Title |
Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae. |
Journal |
|
Related pathway |
rn00280 | Valine, leucine and isoleucine degradation |
rn00523 | Polyketide sugar unit biosynthesis |
|
KO pathway |
|