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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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PKS domain organization and plausible biosynthetic pathway for akaeolide.
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marinedrugs-13-00581-f005: PKS domain organization and plausible biosynthetic pathway for akaeolide.

Mentions: Gene organization of the biosynthetic gene cluster for akaeolide (1) and proposed functions of the PKS genes and the neighboring genes are summarized in Table 2. This gene cluster consists of four PKS genes with eight modules (Figure 4a). AT domains in loading module (LM), module 3 (m3), m5, and m7 have signature amino-acid residues specific to malonyl-CoA (C2), while those of m1, m2, and m4 have that for methylmalonyl-CoA (C3) [12,13]. The signature amino-acid residue of m6 predicted its substrate as an alkylmalonyl-CoA, specifically propylmalonyl-CoA (C5) in this case as suggested by the structure of the product [14,15,16]. These annotation results indicate that the PKSs assemble the polyketide carbon chain by sequential incorporation of C2, C3, C3, C2, C3, C2, C5, and C2 units. In combination with the results from 13C-labeling experiments, we could propose that the chain extension starts from C-16/C-15 acetate unit, followed by a sequence of condensation with two methylmalonates, one malonate, one methylmalonate, one malonate, and one propylmalonate, and terminates at C-18 by incorporation of one malonate (Figure 3). In multimodular type I PKS pathways, combination of DH, ER, and KR domains in each module regulates the oxidation level of carbons in the polyketide chain [5]. This PKS cluster has four DH/KR domains and one DH/ER/KR domain, corresponding to four double bonds and one saturated methylene formation, respectively, but the actual product has only two double bonds. DH domains in m3 and m6 are likely not functional (represented by “dh” in Figure 5). A quite similar gene cluster is present in the genome of Lechevalieria aerocolonigenes NBRC 13195T, which will be discussed later (Figure 4b).


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)

PKS domain organization and plausible biosynthetic pathway for akaeolide.
© Copyright Policy
Related In: Results  -  Collection

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

marinedrugs-13-00581-f005: PKS domain organization and plausible biosynthetic pathway for akaeolide.
Mentions: Gene organization of the biosynthetic gene cluster for akaeolide (1) and proposed functions of the PKS genes and the neighboring genes are summarized in Table 2. This gene cluster consists of four PKS genes with eight modules (Figure 4a). AT domains in loading module (LM), module 3 (m3), m5, and m7 have signature amino-acid residues specific to malonyl-CoA (C2), while those of m1, m2, and m4 have that for methylmalonyl-CoA (C3) [12,13]. The signature amino-acid residue of m6 predicted its substrate as an alkylmalonyl-CoA, specifically propylmalonyl-CoA (C5) in this case as suggested by the structure of the product [14,15,16]. These annotation results indicate that the PKSs assemble the polyketide carbon chain by sequential incorporation of C2, C3, C3, C2, C3, C2, C5, and C2 units. In combination with the results from 13C-labeling experiments, we could propose that the chain extension starts from C-16/C-15 acetate unit, followed by a sequence of condensation with two methylmalonates, one malonate, one methylmalonate, one malonate, and one propylmalonate, and terminates at C-18 by incorporation of one malonate (Figure 3). In multimodular type I PKS pathways, combination of DH, ER, and KR domains in each module regulates the oxidation level of carbons in the polyketide chain [5]. This PKS cluster has four DH/KR domains and one DH/ER/KR domain, corresponding to four double bonds and one saturated methylene formation, respectively, but the actual product has only two double bonds. DH domains in m3 and m6 are likely not functional (represented by “dh” in Figure 5). A quite similar gene cluster is present in the genome of Lechevalieria aerocolonigenes NBRC 13195T, which will be discussed later (Figure 4b).

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