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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.

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Conversion of akaeolide (1) to 17-chloroakaeolide (4).
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marinedrugs-13-00581-f002: Conversion of akaeolide (1) to 17-chloroakaeolide (4).

Mentions: Inspection of the carbon connectivity and the position of carbon branches suggested that 1 and 2 were synthesized through the polyketide pathway. In order to elucidate the biosynthetic origin and incorporation pattern, strain NPS554 was cultured in the presence of plausible biosynthetic precursors labeled with carbon-13, namely [1-13C]acetate, [2-13C]acetate, and [1-13C]propionate, which could be incorporated into the polyketide backbone via acyl CoA carboxylation. According to our previous study, 1 exists as a mixture of several tautomeric isomers in NMR solvents caused by the enolization at C-17, consequently giving multiple 13C signals for each carbon [8]. This was undesirable to the quantification of carbon intensity; therefore, the purified 13C-labeled 1 was converted to the chlorinated derivative 4 which could not undergo isomerization (Figure 2).


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)

Conversion of akaeolide (1) to 17-chloroakaeolide (4).
© Copyright Policy
Related In: Results  -  Collection

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

marinedrugs-13-00581-f002: Conversion of akaeolide (1) to 17-chloroakaeolide (4).
Mentions: Inspection of the carbon connectivity and the position of carbon branches suggested that 1 and 2 were synthesized through the polyketide pathway. In order to elucidate the biosynthetic origin and incorporation pattern, strain NPS554 was cultured in the presence of plausible biosynthetic precursors labeled with carbon-13, namely [1-13C]acetate, [2-13C]acetate, and [1-13C]propionate, which could be incorporated into the polyketide backbone via acyl CoA carboxylation. According to our previous study, 1 exists as a mixture of several tautomeric isomers in NMR solvents caused by the enolization at C-17, consequently giving multiple 13C signals for each carbon [8]. This was undesirable to the quantification of carbon intensity; therefore, the purified 13C-labeled 1 was converted to the chlorinated derivative 4 which could not undergo isomerization (Figure 2).

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