KEGG   PATHWAY: map00253Help
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
BRITE hierarchy
Pathway map
map00253  Tetracycline biosynthesis
map00253

Ortholog table
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
  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
  Authors
Pickens LB, Tang Y
  Title
Oxytetracycline biosynthesis.
  Journal
J Biol Chem 285:27509-15 (2010)
DOI:10.1074/jbc.R110.130419
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
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
  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
  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
  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)
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
J Biol Chem 280:37455-60 (2005)
DOI:10.1074/jbc.M503191200
Reference
  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
  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
  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
  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
KO pathway
ko00253   

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