Cytochrome P450 complement (CYPome) of the avermectin-producer Streptomyces avermitilis and comparison to that of Streptomyces coelicolor A3(2)

doi:10.1016/S0006-291X(03)01231-2

Biochemical and Biophysical Research Communications

Volume 307, Issue 3, 1 August 2003, Pages 610-619

https://doi.org/10.1016/S0006-291X(03)01231-2 Get rights and content

Abstract

The genus Streptomyces produces about two-thirds of naturally occurring antibiotics and a wide array of other secondary metabolites, including antihelminthic agents, antitumor agents, antifungal agents, and herbicides. The newly completed genome sequence of the avermectin-producing bacterium Streptomyces avermitilis contains 33 cytochromes P450 (CYPs), many more than the 18 observed in Streptomyces coelicolor A3(2). Some of the likely metabolic functions are reported together with their genomic location and bioinformatic analysis. Seven entirely new CYP families were found together with close homologues of some forms observed in S. coelicolor A3(2). The presence of unusual CYP forms associated with conservons is revealed and of these, CYP157 forms in both S. avermitilis and S. coelicolor A3(2) deviate from the previously accepted rule for an EXXR motif within the K-helix of CYPs. Amongst this range of CYPs are forms associated with avermectin, filipin, geosmin, and pentalenolactone biosynthesis as well as unknown pathways of secondary metabolism.

Section snippets

Experimental procedures

Database searches and sequence analyses. The S. avermitilis genome database (http://avermitilis.ls.kitasato-u.ac.jp) was first searched using the CYP heme binding domain signature (unusually represented as FXXGXXXCXG, though there are exceptions at all three non-cysteine positions) as query sequence. Genes identified as encoding polypeptides containing such motifs were then screened for the presence of a highly conserved threonine in the putative I-helix, which is proposed to be involved in CYP

Results and discussion

Detection of CYP genes in a genome is greatly facilitated by the presence of consensus amino acid sequences present in all CYPs. Application of such criteria to the genome data of S. avermitilis revealed 33 CYPs. In S. coelicolor A3(2) and S. avermitilis, respectively, CYPs contributed to approximately 0.2% and 0.4% of all the coding sequences. This is a relatively high value for CYP and compares favourably to the 1% contribution of CYPs to the Arabidopsis thaliana genome [24]. The CYP

Conclusions

Genes encoding cytochromes P450 are not usually abundant in bacteria, but 18 CYP genes and 33 CYP genes were identified in S. coelicolor A3(2) and S. avermitilis, respectively. In both organisms, it is proposed that at least one-third of them (11 at least in S. avermitilis) are involved in the biosynthesis of secondary metabolites. Many of the remaining CYP genes probably contribute to secondary metabolite production but are not linked to a specified gene cluster; a few may be involved in

Acknowledgements

We are grateful for support from the Biotechnological and Biological Sciences Research Council, UK, and the Wellcome Trust (D.C.L.) and Grants GM37942 and ES00267 (M.R.W.). We wish to thank Professor David Hopwood, John Innes Centre, UK, for critical reading of the manuscript.

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^☆: Abbreviations: CYP, cytochrome P450; ORF, open reading frame; cvn, conservon; oriC, origin replication; fpr, ferredoxin reductase; fdx, ferredoxin.

¹: Both authors contributed equally to this work.

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Cytochrome P450 complement (CYPome) of the avermectin-producer Streptomyces avermitilis and comparison to that of Streptomyces coelicolor A3(2)☆

Abstract

Section snippets

Experimental procedures

Results and discussion

Conclusions

Acknowledgements

Trends Genet.

Curr. Opin. Microbiol.

Curr. Opin. Biotechnol.

J. Biol. Chem.

Chem. Biol.

FEMS Microbiol. Lett.

Chem. Biol.

Gene

J. Biol. Chem.

FEBS Lett.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Arch. Biochem. Biophys.

The Actinomycetes

An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea

Science

Cloning and heterologous expression of the epothilone gene cluster

Science

Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis

Proc. Natl. Acad. Sci. USA