Limits...
Identification of the Lomofungin Biosynthesis Gene Cluster and Associated Flavin-Dependent Monooxygenase Gene in Streptomyces lomondensis S015.

Zhang C, Sheng C, Wang W, Hu H, Peng H, Zhang X - PLoS ONE (2015)

Bottom Line: Inactivation of lomo10 by in-frame partial deletion resulted in the biosynthesis of a new phenazine metabolite, 1-carbomethoxy-6-formyl-4,9-dihydroxy-phenazine, along with the absence of lomofungin.This result suggests that lomo10 is responsible for the hydroxylation of lomofungin at its C-7 position.This is the first description of a phenazine hydroxylation gene in Streptomyces, and the results of this study lay the foundation for further investigation of phenazine metabolite biosynthesis in Streptomyces.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.

ABSTRACT
Streptomyces lomondensis S015 synthesizes the broad-spectrum phenazine antibiotic lomofungin. Whole genome sequencing of this strain revealed a genomic locus consisting of 23 open reading frames that includes the core phenazine biosynthesis gene cluster lphzGFEDCB. lomo10, encoding a putative flavin-dependent monooxygenase, was also identified in this locus. Inactivation of lomo10 by in-frame partial deletion resulted in the biosynthesis of a new phenazine metabolite, 1-carbomethoxy-6-formyl-4,9-dihydroxy-phenazine, along with the absence of lomofungin. This result suggests that lomo10 is responsible for the hydroxylation of lomofungin at its C-7 position. This is the first description of a phenazine hydroxylation gene in Streptomyces, and the results of this study lay the foundation for further investigation of phenazine metabolite biosynthesis in Streptomyces.

No MeSH data available.


Related in: MedlinePlus

Proposed lomofungin biosynthetic pathway in Streptomyces lomondensis S015.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4549113&req=5

pone.0136228.g007: Proposed lomofungin biosynthetic pathway in Streptomyces lomondensis S015.

Mentions: Based on the alignment of the S. lomondensis S015 genes and the other results obtained in this study, a putative lomofungin biosynthesis pathway is shown in Fig 7. Buckland et al. [51] confirmed that lomofungin is biosynthesized from PDC. Thus, here we propose that the lphzGFDECB gene cluster can biosynthesize PDC. The new compound obtained in this study, 1-carbomethoxy-6-formyl-4,9-dihydroxy-phenazine (compound A), might be synthesized from PDC in several steps catalyzed by Lomo9 and Lomo11 et al., and then converted into lomofungin by lomo10. Further validation of this pathway is required.


Identification of the Lomofungin Biosynthesis Gene Cluster and Associated Flavin-Dependent Monooxygenase Gene in Streptomyces lomondensis S015.

Zhang C, Sheng C, Wang W, Hu H, Peng H, Zhang X - PLoS ONE (2015)

Proposed lomofungin biosynthetic pathway in Streptomyces lomondensis S015.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549113&req=5

pone.0136228.g007: Proposed lomofungin biosynthetic pathway in Streptomyces lomondensis S015.
Mentions: Based on the alignment of the S. lomondensis S015 genes and the other results obtained in this study, a putative lomofungin biosynthesis pathway is shown in Fig 7. Buckland et al. [51] confirmed that lomofungin is biosynthesized from PDC. Thus, here we propose that the lphzGFDECB gene cluster can biosynthesize PDC. The new compound obtained in this study, 1-carbomethoxy-6-formyl-4,9-dihydroxy-phenazine (compound A), might be synthesized from PDC in several steps catalyzed by Lomo9 and Lomo11 et al., and then converted into lomofungin by lomo10. Further validation of this pathway is required.

Bottom Line: Inactivation of lomo10 by in-frame partial deletion resulted in the biosynthesis of a new phenazine metabolite, 1-carbomethoxy-6-formyl-4,9-dihydroxy-phenazine, along with the absence of lomofungin.This result suggests that lomo10 is responsible for the hydroxylation of lomofungin at its C-7 position.This is the first description of a phenazine hydroxylation gene in Streptomyces, and the results of this study lay the foundation for further investigation of phenazine metabolite biosynthesis in Streptomyces.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.

ABSTRACT
Streptomyces lomondensis S015 synthesizes the broad-spectrum phenazine antibiotic lomofungin. Whole genome sequencing of this strain revealed a genomic locus consisting of 23 open reading frames that includes the core phenazine biosynthesis gene cluster lphzGFEDCB. lomo10, encoding a putative flavin-dependent monooxygenase, was also identified in this locus. Inactivation of lomo10 by in-frame partial deletion resulted in the biosynthesis of a new phenazine metabolite, 1-carbomethoxy-6-formyl-4,9-dihydroxy-phenazine, along with the absence of lomofungin. This result suggests that lomo10 is responsible for the hydroxylation of lomofungin at its C-7 position. This is the first description of a phenazine hydroxylation gene in Streptomyces, and the results of this study lay the foundation for further investigation of phenazine metabolite biosynthesis in Streptomyces.

No MeSH data available.


Related in: MedlinePlus