Limits...
Biosynthesis of akaeolide and lorneic acids and annotation of type I polyketide synthase gene clusters in the genome of Streptomyces sp. NPS554.

Zhou T, Komaki H, Ichikawa N, Hosoyama A, Sato S, Igarashi Y - Mar Drugs (2015)

Bottom Line: The putative gene clusters contain all the polyketide synthase (PKS) domains necessary for assembly of the carbon skeletons.Combined with the 13C-labeling results, gene function prediction enabled us to propose biosynthetic pathways involving unusual carbon-carbon bond formation reactions.Genome analysis also indicated the presence of at least ten orphan type I PKS gene clusters that might be responsible for the production of new polyketides.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan. t276001@st.pu-toyama.ac.jp.

ABSTRACT
The incorporation pattern of biosynthetic precursors into two structurally unique polyketides, akaeolide and lorneic acid A, was elucidated by feeding experiments with 13C-labeled precursors. In addition, the draft genome sequence of the producer, Streptomyces sp. NPS554, was performed and the biosynthetic gene clusters for these polyketides were identified. The putative gene clusters contain all the polyketide synthase (PKS) domains necessary for assembly of the carbon skeletons. Combined with the 13C-labeling results, gene function prediction enabled us to propose biosynthetic pathways involving unusual carbon-carbon bond formation reactions. Genome analysis also indicated the presence of at least ten orphan type I PKS gene clusters that might be responsible for the production of new polyketides.

Show MeSH
Structures of akaeolide (1) and lorneic acids A (2) and B (3).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4306953&req=5

marinedrugs-13-00581-f001: Structures of akaeolide (1) and lorneic acids A (2) and B (3).

Mentions: In our previous studies, two new unique polyketide classes, akaeolide (1) and lorneic acids A (2) and B (3) were isolated from Streptomyces sp. NPS554 collected from marine sediment near the coast of Miyazaki, Japan (Figure 1). Akaeolide (1) has an unusual 15-membered carbocyclic framework containing a β-keto-δ-lactone unit [8]. This compound displays moderate antimicrobial activity against Micrococcus luteus with an MIC value of 25 μg/mL (64 μM) and cytotoxicity to 3Y1 rat fibroblasts with an IC50 value of 8.5 μM. Lorneic acids have a fatty acid-like structure in which a benzene ring is embedded. They inhibit phosphodiesterases with selectivity toward PDE5 with IC50 values of submicromolar range [9]. Despite the structural rarity of these compounds, biosynthetic origins remain unknown. We herein report the biosynthesis of akaeolide and lorneic acid elucidated by isotope precursor feeding and by annotation of biosynthetic genes. Annotation of unknown type I PKS gene clusters responsible for the production of new polyketides is also presented.


Biosynthesis of akaeolide and lorneic acids and annotation of type I polyketide synthase gene clusters in the genome of Streptomyces sp. NPS554.

Zhou T, Komaki H, Ichikawa N, Hosoyama A, Sato S, Igarashi Y - Mar Drugs (2015)

Structures of akaeolide (1) and lorneic acids A (2) and B (3).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4306953&req=5

marinedrugs-13-00581-f001: Structures of akaeolide (1) and lorneic acids A (2) and B (3).
Mentions: In our previous studies, two new unique polyketide classes, akaeolide (1) and lorneic acids A (2) and B (3) were isolated from Streptomyces sp. NPS554 collected from marine sediment near the coast of Miyazaki, Japan (Figure 1). Akaeolide (1) has an unusual 15-membered carbocyclic framework containing a β-keto-δ-lactone unit [8]. This compound displays moderate antimicrobial activity against Micrococcus luteus with an MIC value of 25 μg/mL (64 μM) and cytotoxicity to 3Y1 rat fibroblasts with an IC50 value of 8.5 μM. Lorneic acids have a fatty acid-like structure in which a benzene ring is embedded. They inhibit phosphodiesterases with selectivity toward PDE5 with IC50 values of submicromolar range [9]. Despite the structural rarity of these compounds, biosynthetic origins remain unknown. We herein report the biosynthesis of akaeolide and lorneic acid elucidated by isotope precursor feeding and by annotation of biosynthetic genes. Annotation of unknown type I PKS gene clusters responsible for the production of new polyketides is also presented.

Bottom Line: The putative gene clusters contain all the polyketide synthase (PKS) domains necessary for assembly of the carbon skeletons.Combined with the 13C-labeling results, gene function prediction enabled us to propose biosynthetic pathways involving unusual carbon-carbon bond formation reactions.Genome analysis also indicated the presence of at least ten orphan type I PKS gene clusters that might be responsible for the production of new polyketides.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan. t276001@st.pu-toyama.ac.jp.

ABSTRACT
The incorporation pattern of biosynthetic precursors into two structurally unique polyketides, akaeolide and lorneic acid A, was elucidated by feeding experiments with 13C-labeled precursors. In addition, the draft genome sequence of the producer, Streptomyces sp. NPS554, was performed and the biosynthetic gene clusters for these polyketides were identified. The putative gene clusters contain all the polyketide synthase (PKS) domains necessary for assembly of the carbon skeletons. Combined with the 13C-labeling results, gene function prediction enabled us to propose biosynthetic pathways involving unusual carbon-carbon bond formation reactions. Genome analysis also indicated the presence of at least ten orphan type I PKS gene clusters that might be responsible for the production of new polyketides.

Show MeSH