Lorneic acids C and D, new trialkyl-substituted aromatic acids isolated from a terrestrial Streptomyces sp.

Raju, Ritesh; Gromyko, Oleksandr; Fedorenko, V. O.; Luzhetskyy, Andriy; Müller, Rolf

doi:10.1038/ja.2013.18

Cited by 11 publications

(5 citation statements)

References 4 publications

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“…Both extracts were combined and then applied on a repeated silica gel chromatograph column (CC), Sephadex LH-20 column, preparative HPLC, and semipreparative HPLC to yield six new lorneic acids E−J (1−6) as well as two known lorneic acids K (7) 11 and D (8) (Chart 1). 14 Lorneic acid E (1) was obtained as colorless oil. Its molecular formula was deduced to be C 17 H 22 O 3 by HRESIMS.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Lorneic Acid Analogues from an Endophytic Actinomycete

Yang

Yang²,

Wang

et al. 2017

J. Nat. Prod.

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Our natural products discovery program utilizes endophytic actinomycetes associated with plants and employs biological assays and HPLC-based metabolite profiles as the preliminary screen to identify strains of interest, followed by large-scale fermentation and isolation, leading to new and/or bioactive natural products. Six new trialkyl-substituted aromatic acids, namely, lorneic acids E-J (1-6), together with two known analogues (7 and 8), were isolated and identified from the culture extract of Streptomyces sp. KIB-H1289, an endophytic actinomycete obtained from the inner tissue of the bark of Betula mandshurica Nakai. The structures were characterized by interpretation of their spectroscopic data, mainly 1D and 2D NMR. Among them, compound 5 contains a unique disulfide bond that is presumably derived from N-acetylcysteine. All isolated metabolites were evaluated for their inhibitory activity on tyrosinase.

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Section: ■ Results and Discussionmentioning

confidence: 99%

“…CC12J (GeneBank no: KM187147.1). In this context, we describe the compound isolation and structural elucidation of new lorneic acid − analogues 1 – 6 , as well as their inhibitory effects on tyrosinase.…”

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confidence: 99%

Lorneic Acid Analogues from an Endophytic Actinomycete

Yang

Yang²,

Wang

et al. 2017

J. Nat. Prod.

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“…Attractively, there are a group of trialkyl-substituted aromatic polyketides derived from the type I PKSs in Streptomyces, structurally featuring with a benzene core in the middle of polyketide chain such as TM-123/veramycin B (1), veramycin A (2), NFAT-133 (3), benwamycin I (4), lorneic acids, and gombapyrones [5][6][7][8][9][10] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of trialkyl-substituted aromatic polyketide NFAT-133 involves unusual aromatization-mediating P450 monooxygenase and metallo-beta- lactamase fold thioesterase

Yang

Zhou

et al. 2023

Preprint

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Background The bacterial trialkyl-substituted aromatic polyketides are biosynthetically unique due to the unusual P450 monooxygenase-mediated aromatic core formation in the polyketide chains offloaded from type I polyketide synthase (PKS). As the representatives, TM-123 (1), veramycin A (2), NFAT-133 (3), and benwamycin I (4) were discovered from several Streptomyces species and they were characterized with antidiabetic and immunosuppressant activities. Though the biosynthesis of 1 − 3 were verified to be directed by the NFAT-133 biosynthetic gene cluster (nft BGC), it remains a mystery how 3 was generated during the biosynthesis. Results The biosynthesis of compounds 1 − 4 was verified to be directed by a cognate nft BGC in Streptomyces conglobatus. The PKS assembly logic of 1 − 4 was revised according to site-mutagenetic analysis of three PKS dehydratase domains. Gene deletion and mutant complementation of the five genes in nft BGC confirmed two essential genes of P450 monooxygenase nftE1 and metallo-beta-lactamase (MBL) fold hydrolase nftF1. Deletion of nftE1 led to abolishment of 1 − 4 and accumulation of four new products (5 − 8). Structural elucidation reveals 5 − 8 as the non-aromatic analogs of 1. Deletion of nftF1 gene resulted in disappearance of 3 and 4, while the production of 1 and 2 was not interrupted. Protein sequence analysis and structure-modeling by AlphaFold2 indicate that NftF1 is a MBL fold hydrolase. In vivo site-directed mutagenesis allowed identification of eight key residues in its active sites. Conclusion The PKS assembly logic of nft BGC is revised according to site-directed mutagenetic analysis. The benzene core of 1 − 4 should be formed through a NftE1-catalyzed oxidative-aromatization on the polyene chains offloaded from PKS. NftF1 should serve as a trans-acting thioesterase (TE) to mediate a premature chain-offloading from ACP7 to yield the nascent chain of compound 3. The key residues in the predicted active site of NftE1 were identified by in vivo site-directed mutations. Though the NftE1 homologs are widespread in type II PKSs, their functions are underexplored. As far as we know, NftE1 should represent the first MBL fold TE discovered from type I PKS.

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“…The aromatic polyketides derived from type I PKSs normally contain the terminal benzyl ring derived from the starting building block of PKS assembly [ 4 ]. Attractively, there are a group of trialkyl-substituted aromatic polyketides derived from type I PKSs in Streptomyces , structurally featuring with a benzene core in the middle of polyketide chain such as TM-123/veramycin B ( 1 ), veramycin A ( 2 ), NFAT-133 ( 3 ), benwamycin I ( 4 ), lorneic acids, and gombapyrones [ [5] , [6] , [7] , [8] , [9] , [10] ] ( Fig. 1 ).…”

Section: Introductionmentioning

confidence: 99%