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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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Proposed biosynthetic pathway for lorneic acids.
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marinedrugs-13-00581-f007: Proposed biosynthetic pathway for lorneic acids.

Mentions: Gene organization of the biosynthetic gene cluster for lorneic acids (2 and 3) is shown in Figure 6 and proposed functions of the PKS genes and the neighboring genes are summarized in Table 3. The PKS gene cluster is composed of one loading module and seven extension modules (Figure 7). Signature amino-acid residues of AT domains [12,13] predicted the substrate specificity: acetyl-CoA (C2) would be loaded onto LM, malonyl-CoA (C2) onto m1, m2, m3, m5, m6, and m7, and methylmalonyl-CoA (C3) onto m4. Therefore, the polyketide carbon chain would be assembled by sequential incorporation of C2, C2, C2, C2, C3, C2, C2, and C2 units, consistent with the results obtained from the 13C-labeling experiments (Figure 3). The PKS cluster contains three DH/ER/KR domains in m1, m2, and m4 and four DH/KR domains in m3, m5, m6, and m7, corresponding to three saturated methylene carbons and four double bonds, respectively. However, the ER domain in m4 might be unfunctional if a putative intermediate A (Figure 7) were generated as described below [22].


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)

Proposed biosynthetic pathway for lorneic acids.
© Copyright Policy
Related In: Results  -  Collection

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

marinedrugs-13-00581-f007: Proposed biosynthetic pathway for lorneic acids.
Mentions: Gene organization of the biosynthetic gene cluster for lorneic acids (2 and 3) is shown in Figure 6 and proposed functions of the PKS genes and the neighboring genes are summarized in Table 3. The PKS gene cluster is composed of one loading module and seven extension modules (Figure 7). Signature amino-acid residues of AT domains [12,13] predicted the substrate specificity: acetyl-CoA (C2) would be loaded onto LM, malonyl-CoA (C2) onto m1, m2, m3, m5, m6, and m7, and methylmalonyl-CoA (C3) onto m4. Therefore, the polyketide carbon chain would be assembled by sequential incorporation of C2, C2, C2, C2, C3, C2, C2, and C2 units, consistent with the results obtained from the 13C-labeling experiments (Figure 3). The PKS cluster contains three DH/ER/KR domains in m1, m2, and m4 and four DH/KR domains in m3, m5, m6, and m7, corresponding to three saturated methylene carbons and four double bonds, respectively. However, the ER domain in m4 might be unfunctional if a putative intermediate A (Figure 7) were generated as described below [22].

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