Entry Name Tetracycline biosynthesis
Description Tetracyclines are aromatic polyketide antibiotics produced by Streptomyces species via type II polyketide synthases (PKSs). Tetracyclines contain a linear tetracyclic skeleton, which is formed from a malonamate starter unit and malonyl-CoA extender units through a common polyketide pathway [MD:
M00778 ]. This diagram shows biosynthesis of naturally occurring tetracyclines (tetracycline, oxytetracycline and chlortetracycline) via a common intermediate anhydrotetracycline [MD:
M00780 M00823 ].
Class Metabolism; Metabolism of terpenoids and polyketidesBRITE hierarchy
Pathway map Module M00778 Type II polyketide backbone biosynthesis, acyl-CoA + malonyl-CoA => polyketide [PATH:ko00253 ]
M00780 Tetracycline/oxytetracycline biosynthesis, pretetramide => tetracycline/oxytetracycline [PATH:ko00253 ]
M00823 Chlortetracycline biosynthesis, pretetramide => chlortetracycline [PATH:ko00253 ]
Drug D00201 Tetracycline (JAN/USP/INN)
D07689 Chlortetracycline (INN)
Other DBs Orthology K05552 actI2, oxyB, tcmL, snoa2, aknC, mtmK; minimal PKS chain-length factor (CLF/KS beta) [EC:2.3.1.- 2.3.1.260 2.3.1.235 ]
K05553 actI3, oxyC, tcmM, snoa3, aknD, mtmS; minimal PKS acyl carrier protein
K12420 actIII, oxyJ, snoaD, aknA; ketoreductase [EC:1.1.1.-]
K14244 oxyD; amidotransferase [EC:6.3.5.-]
K14249 oxyK; bifunctional cyclase/aromatase [EC:4.2.1.-]
K14250 oxyN, snoaM, dpsY, aknW, mtmY; cyclase
K14251 oxyF; C-methyltransferase [EC:2.1.1.-]
K14255 oxyT, ctcO, cts6; 4-amino-anhydrotetracycline N4-methyltransferase [EC:2.1.1.335 ]
K14257 ctcP, cts4, prnC; tetracycline 7-halogenase / FADH2 O2-dependent halogenase [EC:1.14.19.49 1.14.19.-]
K18221 tetX; tetracycline 11a-monooxygenase, tetracycline resistance protein [EC:1.14.13.231 ]
Compound C01209 Malonyl-[acyl-carrier protein]
C03206 5a,11a-Dehydrotetracycline
C06627 4-Keto-anhydrotetracycline
C06628 4-Hydroxy-6-methylpretetramide
C06654 4-Amino-anhydrotetracycline
C12441 18-Carbamoyl-3,5,7,9,11,13,15,17-octaoxooctadecanoyl-[acp]
C12442 C-9 Reduced nonaketamide
C18293 Nonaketamide monocyclic intermediate
C18294 Nonaketamide tricyclic intermediate
C18296 5a,11a-Dehydrooxytetracycline
C21391 11a-Hydroxytetracycline
C21430 Malonamoyl-[acyl-carrier protein]
C21438 11a-Hydroxyoxytetracycline
C21439 11a-Hydroxy-7-chlortetracycline
Reference Authors Petkovic H, Cullum J, Hranueli D, Hunter IS, Peric-Concha N, Pigac J, Thamchaipenet A, Vujaklija D, Long PF
Title Genetics of Streptomyces rimosus, the oxytetracycline producer.
Journal Reference Authors Pickens LB, Tang Y
Title Oxytetracycline biosynthesis.
Journal Reference Authors Zhang W, Ames BD, Tsai SC, Tang Y
Title Engineered biosynthesis of a novel amidated polyketide, using the malonamyl-specific initiation module from the oxytetracycline polyketide synthase.
Journal Reference Authors Dewick PM.
Title Medicinal Natural Products: A Biosynthetic Approach, Second Edition
Journal John Wiley and Sons (2001)
Reference Authors Miller PA, Hash JH
Title S-adenosylmethionine:dedimethylamino-4-aminoanhydrotetracycline N-methyltransferase.
Journal Reference Authors Miller PA, Hash JH
Title ADP; tetracyclin 5a(11a)dehydrogenase.
Journal Reference Authors Wang P, Zhang W, Zhan J, Tang Y
Title Identification of OxyE as an ancillary oxygenase during tetracycline biosynthesis.
Journal Reference Authors Zhang W, Watanabe K, Cai X, Jung ME, Tang Y, Zhan J
Title Identifying the minimal enzymes required for anhydrotetracycline biosynthesis.
Journal Reference Authors Petkovic H, Thamchaipenet A, Zhou LH, Hranueli D, Raspor P, Waterman PG, Hunter IS
Title Disruption of an aromatase/cyclase from the oxytetracycline gene cluster of Streptomyces rimosus results in production of novel polyketides with shorter chain lengths.
Journal Reference Authors Peric-Concha N, Borovicka B, Long PF, Hranueli D, Waterman PG, Hunter IS
Title Ablation of the otcC gene encoding a post-polyketide hydroxylase from the oxytetracyline biosynthetic pathway in Streptomyces rimosus results in novel polyketides with altered chain length.
Journal Reference Authors Zhang W, Watanabe K, Wang CC, Tang Y
Title Investigation of early tailoring reactions in the oxytetracycline biosynthetic pathway.
Journal Reference Authors Kim ES, Bibb MJ, Butler MJ, Hopwood DA, Sherman DH.
Title Sequences of the oxytetracycline polyketide synthase-encoding otc genes from Streptomyces rimosus.
Journal Reference Authors Dairi T, Nakano T, Aisaka K, Katsumata R, Hasegawa M.
Title Cloning and nucleotide sequence of the gene responsible for chlorination of tetracycline.
Journal Reference Authors Wang P, Bashiri G, Gao X, Sawaya MR, Tang Y
Title Uncovering the enzymes that catalyze the final steps in oxytetracycline biosynthesis.
Journal Reference Authors Zhu T, Cheng X, Liu Y, Deng Z, You D
Title Deciphering and engineering of the final step halogenase for improved chlortetracycline biosynthesis in industrial Streptomyces aureofaciens.
Journal Reference Authors Yang W, Moore IF, Koteva KP, Bareich DC, Hughes DW, Wright GD
Title TetX is a flavin-dependent monooxygenase conferring resistance to tetracycline antibiotics.
Journal Related ko01056 Biosynthesis of type II polyketide backbone
