KEGG PATHWAY: map00253

PATHWAY: map00253

Entry

map00253                    Pathway

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 polyketides

Pathway map

map00253

Tetracycline biosynthesis

Module

M00778

Type II polyketide backbone biosynthesis, acyl-CoA + malonyl-CoA => polyketide [PATH:map00253]

M00780

Tetracycline/oxytetracycline biosynthesis, pretetramide => tetracycline/oxytetracycline [PATH:map00253]

M00823

Chlortetracycline biosynthesis, pretetramide => chlortetracycline [PATH:map00253]

Drug

D00201

Tetracycline (JAN/USP/INN)

D07689

Chlortetracycline (INN)

Other DBs

GO:

0043644

Reference

PMID:16959966

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

Microbiol Mol Biol Rev 70:704-28 (2006)
DOI:10.1128/MMBR.00004-06

Reference

PMID:20522541

Authors

Pickens LB, Tang Y

Title

Oxytetracycline biosynthesis.

Journal

J Biol Chem 285:27509-15 (2010)
DOI:10.1074/jbc.R110.130419

Reference

PMID:16597959

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

Appl Environ Microbiol 72:2573-80 (2006)
DOI:10.1128/AEM.72.4.2573-2580.2006

Reference

Authors

Dewick PM.

Title

Medicinal Natural Products: A Biosynthetic Approach, Second Edition

Journal

John Wiley and Sons (2001)

Reference

PMID:1134373

Authors

Miller PA, Hash JH

Title

S-adenosylmethionine:dedimethylamino-4-aminoanhydrotetracycline N-methyltransferase.

Journal

Methods Enzymol 43:603-6 (1975)
DOI:10.1016/0076-6879(75)43122-6

Reference

PMID:1134374

Authors

Miller PA, Hash JH

Title

ADP; tetracyclin 5a(11a)dehydrogenase.

Journal

Methods Enzymol 43:606-7 (1975)
DOI:10.1016/0076-6879(75)43123-8

Reference

PMID:19472250

Authors

Wang P, Zhang W, Zhan J, Tang Y

Title

Identification of OxyE as an ancillary oxygenase during tetracycline biosynthesis.

Journal

Chembiochem 10:1544-50 (2009)
DOI:10.1002/cbic.200900122

Reference

PMID:18422316

Authors

Zhang W, Watanabe K, Cai X, Jung ME, Tang Y, Zhan J

Title

Identifying the minimal enzymes required for anhydrotetracycline biosynthesis.

Journal

J Am Chem Soc 130:6068-9 (2008)
DOI:10.1021/ja800951e

Reference

PMID:10551844

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

J Biol Chem 274:32829-34 (1999)
DOI:10.1016/S0021-9258(17)46583-5

Reference

PMID:16148009

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

J Biol Chem 280:37455-60 (2005)
DOI:10.1074/jbc.M503191200

Reference

PMID:17631493

Authors

Zhang W, Watanabe K, Wang CC, Tang Y

Title

Investigation of early tailoring reactions in the oxytetracycline biosynthetic pathway.

Journal

J Biol Chem 282:25717-25 (2007)
DOI:10.1074/jbc.M703437200

Reference

PMID:8163168

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

Gene 141:141-2 (1994)
DOI:10.1016/0378-1119(94)90144-9

Reference

PMID:7612997

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

Biosci Biotechnol Biochem 59:1099-106 (1995)
DOI:10.1271/bbb.59.1099

Reference

PMID:23621493

Authors

Wang P, Bashiri G, Gao X, Sawaya MR, Tang Y

Title

Uncovering the enzymes that catalyze the final steps in oxytetracycline biosynthesis.

Journal

J Am Chem Soc 135:7138-41 (2013)
DOI:10.1021/ja403516u

Reference

PMID:23800859

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

Metab Eng 19:69-78 (2013)
DOI:10.1016/j.ymben.2013.06.003

Reference

PMID:15452119

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

J Biol Chem 279:52346-52 (2004)
DOI:10.1074/jbc.M409573200

Related
pathway

map01056

Biosynthesis of type II polyketide backbone

map07019

Tetracyclines

KO pathway

ko00253

All links

Pathway (3)   
   KEGG MODULE (3)   
Chemical substance (21)   
   KEGG COMPOUND (21)   
Chemical reaction (29)   
   KEGG ENZYME (9)   
   KEGG REACTION (20)   
Gene (171)   
   KEGG ORTHOLOGY (17)   
   RefGene (154)   
Literature (15)   
   PubMed (15)   
All databases (239)   

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