BGC0000024

General information about the BGC

MIBiG accession	BGC0000024
Short description	aureothin biosynthetic gene cluster from Streptomyces thioluteus
Status	Minimal annotation: no A minimal annotation only contains information on the BGC loci and one or more linked chemical product(s) Completeness: complete Whether the loci encodes everything needed for the pathway producing the compound(s)
Biosynthetic class(es)	Polyketide (Polyene)
Loci	NCBI GenBank: AJ575648.1
Compounds	aureothin
Species	Streptomyces thioluteus [taxonomy]
References	Chemical studies on a toxic product of Streptomyces thioluteus, aureothin. WASHIZU F et al., J Antibiot (Tokyo) (1954) PMID:13174453 Identification of mycolutein and pulvomycin as aureothin and labilomycin respectively. Schwartz JL et al., J Antibiot (Tokyo) (1976) PMID:770405 Gamma-pyrone compounds with selective and potent anti-Helicobacter pylori activity. Taniguchi M et al., J Antibiot (Tokyo) (2000) PMID:11079808 Iteration as programmed event during polyketide assembly; molecular analysis of the aureothin biosynthesis gene cluster. He J et al., Chem Biol (2003) PMID:14700630 Biosynthetic origin of the rare nitroaryl moiety of the polyketide antibiotic aureothin: involvement of an unprecedented N-oxygenase. He J et al., J Am Chem Soc (2004) PMID:15038705 Formation of the aureothin tetrahydrofuran ring by a bifunctional cytochrome p450 monooxygenase. He J et al., J Am Chem Soc (2004) PMID:15612710 Mutasynthesis of aureonitrile: an aureothin derivative with significantly improved cytostatic effect. Ziehl M et al., Angew Chem Int Ed Engl (2005) PMID:15645471 Functional analysis of the aureothin iterative type I polyketide synthase. He J et al., Chembiochem (2005) PMID:15812854 Dissection of the late steps in aureothin biosynthesis. Müller M et al., Chembiochem (2006) PMID:16292785 AurF from Streptomyces thioluteus and a possible new family of manganese/iron oxygenases. Krebs C et al., Biochemistry (2007) PMID:17718517 Non-colinear polyketide biosynthesis in the aureothin and neoaureothin pathways: an evolutionary perspective. Traitcheva N et al., Chembiochem (2007) PMID:17763486 Structure and action of the N-oxygenase AurF from Streptomyces thioluteus. Zocher G et al., J Mol Biol (2007) PMID:17765264 In vitro reconstitution and crystal structure of p-aminobenzoate N-oxygenase (AurF) involved in aureothin biosynthesis. Choi YS et al., Proc Natl Acad Sci U S A (2008) PMID:18458342 Four-electron oxidation of p-hydroxylaminobenzoate to p-nitrobenzoate by a peroxodiferric complex in AurF from Streptomyces thioluteus. Li N et al., Proc Natl Acad Sci U S A (2010) PMID:20798054 Structural fine-tuning of a multifunctional cytochrome P450 monooxygenase. Zocher G et al., J Am Chem Soc (2011) PMID:21280577 A ribonucleotide reductase-like electron transfer system in the nitroaryl-forming N-oxygenase AurF. Fries A et al., Chembiochem (2011) PMID:21678538 Interchenar retrotransfer of aureothin intermediates in an iterative polyketide synthase module. Busch B et al., J Am Chem Soc (2012) PMID:22799266 Multifactorial control of iteration events in a modular polyketide assembly line. Busch B et al., Angew Chem Int Ed Engl (2013) PMID:23606628 Rational design of modular polyketide synthases: morphing the aureothin pathway into a luteoreticulin assembly line. Sugimoto Y et al., Angew Chem Int Ed Engl (2014) PMID:24402879 Characterization of the N-oxygenase AurF from Streptomyces thioletus. Chanco E et al., Bioorg Med Chem (2014) PMID:24973817 Exploiting enzymatic promiscuity to engineer a focused library of highly selective antifungal and antiproliferative aureothin analogues. Werneburg M et al., J Am Chem Soc (2010) PMID:20662518

Chemical products information

aureothin

Copy SMILES

C₂₂H₂₃N₁O₆

Chemical database entries
PubCHEM
ChemSpider

List of genes involved in compound(s) production

Identifiers	Position	Product	Functions	Evidence	Extra
CAE02599.1 aurD	2154 - 2969 (+)	AurD protein			copy AA seq copy Nt seq
CAE02600.1 aurE	3029 - 4546 (-)	p-nitrobenzoate CoA ligase	Precursor biosynthesis	Knock-out Other in vivo study	copy AA seq copy Nt seq
CAE02601.1 aurF	4858 - 5868 (+)	p-aminobenzoate N-oxygenase	Precursor biosynthesis	Activity assay Heterologous expression Knock-out Other in vivo study	copy AA seq copy Nt seq
CAE02602.1 aurA	5990 - 11710 (+)	polyketide synthase type I			copy AA seq copy Nt seq
CAE02603.1 aurG	11745 - 13832 (+)	PABA synthase			copy AA seq copy Nt seq
CAE02604.1 aurH	13938 - 15158 (+)	bifunctional cytochrome P450 monooxygenase	Tailoring (Oxidation)	Activity assay Heterologous expression Knock-out Other in vivo study	copy AA seq copy Nt seq
CAE02605.1 aurB	15244 - 21738 (+)	polyketide synthase type I			copy AA seq copy Nt seq
CAE02606.1 aurC	21801 - 28406 (+)	polyketide synthase type I			copy AA seq copy Nt seq
CAE02607.1 aurI	28440 - 29132 (+)	O-methyl transferase	Tailoring (Methylation)	Knock-out Other in vivo study	copy AA seq copy Nt seq

Polyketide-specific information

Subclass	Polyene
Starter unit	p-Nitrobenzoate
Cyclic?	no
Release type	Macrolactamization

Polyketide-synthases

Genes	Properties	Modules
aurB + aurC + aurA	Synthase subclass: Modular type I	Module 1 Specificity: Methylmalonyl-CoA Genes: aurA Core domains: Ketosynthase, Acyltransferase, Ketoreductase, Dehydratase, Thiolation (ACP/PCP) KR-domain stereochemistry: L-OH Non-canonical activity: Iterated Evidence for non-canonical activity:
		Module 2 Specificity: Malonyl-CoA Evidence for specificity: Sequence-based prediction Genes: aurB Core domains: Ketosynthase, Acyltransferase, Ketoreductase, Dehydratase, Enoylreductase, Thiolation (ACP/PCP) KR-domain stereochemistry: L-OH
		Module 3 Specificity: Methylmalonyl-CoA Evidence for specificity: Sequence-based prediction Genes: aurC Core domains: Ketosynthase, Acyltransferase, Thiolation (ACP/PCP)
		Module 4 Genes: aurC Core domains: Ketosynthase, Thiolation (ACP/PCP)

Annotation changelog

MIBiG version	Submitter	Notes
1.0	Hidden contributor (ID: F65XGYSSLMUEJC2Q4T3BLCPS, no GDPR consent given).	Submitted
2.0	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Migrated from v1.4
3.0	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Removed ketoreductase stereochemistry annotation from modules without ketoreductases Updated bioactivity data
3.1	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Update chemical activity to schema version 2.11

Detailed domain annotation

Selected features only

Show module domains

Similar known gene clusters

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