Ulleungamides A and B, Modified α,β-Dehydropipecolic Acid Containing Cyclic Depsipeptides from <i>Streptomyces</i> sp. KCB13F003

Son, Sangkeun; Ko, Sung-Kyun; Jang, Mina; Lee, Jae Kyoung; Ryoo, In‐Ja; Lee, Jung-Sook; Lee, Kyung Ho; Soung, Nak-Kyun; Oh, Hyuncheol; Hong, Young-Shick; Kim, Bo Yeon; Jang, Jae‐Hyuk; Ahn, Jong Seog

doi:10.1021/acs.orglett.5b01969

Cited by 29 publications

(18 citation statements)

References 23 publications

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“…For example damipipecolin, a bromopyrrole alkaloid isolated from the sponge Axinella damicornis, displayed a modulating effect on the serotonin receptor (9); halichonadin K, a dimeric sesquiterpenoid isolated from a marine sponge (Halichondria sp. ), had cytotoxicity against human epidermoid carcinoma KB cells (10); and ulleungamide A, a cyclic depsipeptide isolated from a Streptomyces sp., displayed growthinhibitory activity against some bacteria (8). Thus, there may be an increasing demand for trans-4-L-HyPip, and our production method is promising for its high efficiency and regio-and stereoselectivity.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, 5-hydroxypipecolic acid was found to be present in mammalian brain and blood (5). HyPips are also components of some peptide antibiotics, terpenoids, and alkaloids, for example, trans-3-hydroxy-L-pipecolic acid (trans-3-L-HyPip) in GE81112 (6), cis-3-hydroxy-L-pipecolic acid (cis-3-L-HyPip) in tetrazomine (7), trans-4-hydroxy-L-pipecolic acid (trans-4-L-HyPip) in ulleungamides (8) and damipipecolin (9), and cis-4-hydroxy-L-pipecolic acid (cis-4-L-HyPip) in halichonadins (10).…”

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Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans -4-Hydroxylation of l -Pipecolic Acid

Hibi

Mori

Miyake

et al. 2016

Appl Environ Microbiol

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Hydroxypipecolic acids are bioactive compounds widely distributed in nature and are valuable building blocks for the organic synthesis of pharmaceuticals. We have found a novel hydroxylating enzyme with activity toward L-pipecolic acid (L-Pip) in a filamentous fungus, Fusarium oxysporum c8D. The enzyme L-Pip trans-4-hydroxylase (Pip4H) of F. oxysporum (FoPip4H) belongs to the Fe(II)/␣-ketoglutarate-dependent dioxygenase superfamily, catalyzes the regio-and stereoselective hydroxylation of L-Pip, and produces optically pure trans-4-hydroxy-L-pipecolic acid (trans-4-L-HyPip). Amino acid sequence analysis revealed several fungal enzymes homologous with FoPip4H, and five of these also had L-Pip trans-4-hydroxylation activity. In particular, the homologous Pip4H enzyme derived from Aspergillus nidulans FGSC A4 (AnPip4H) had a broader substrate specificity spectrum than other homologues and reacted with the L and D forms of various cyclic and aliphatic amino acids. Using FoPip4H as a biocatalyst, a system for the preparative-scale production of chiral trans-4-L-HyPip was successfully developed. Thus, we report a fungal family of L-Pip hydroxylases and the enzymatic preparation of trans-4-L-HyPip, a bioactive compound and a constituent of secondary metabolites with useful physiological activities.H ydroxypipecolic acids (HyPips) are naturally occurring sixmembered heterocyclic hydroxy amino acids that are widely distributed in nature. For instance, 4-hydroxy-, 5-hydroxy-, and 4,5-dihydroxypipecolic acids have been found in various members of the plant family (1-4). Likewise, 5-hydroxypipecolic acid was found to be present in mammalian brain and blood (5). HyPips are also components of some peptide antibiotics, terpenoids, and alkaloids, for example, Thus, the enzymatic hydroxylation of L-Pip was achieved as a side reaction of L-proline hydroxylase. To date, specific L-Piphydroxylating enzymes have not been reported, despite the fact that HyPips are important metabolites found in plants and mammals. In the present study, we identified and characterized L-Pip hydroxylases broadly conserved in some filamentous fungi. We found that the newly discovered L-Pip hydroxylases were particularly suitable biocatalysts for the asymmetric hydroxylation of cyclic amino acids, such as pipecolic acids and prolines. Moreover, the widespread distribution of genes encoding L-Pip hydroxylases indicates some important physiological roles of fungal secondary metabolites related to trans-4-L-HyPip. MATERIALS AND METHODSStrains and culture. Microorganisms isolated from soil and plant samples were cultured in GP medium comprised of 0.15% (wt/vol) KH 2 PO 4 , 0.05% (wt/vol) K 2 HPO 4 , 0.1% (wt/vol) NH 4 Cl, 0.03% (wt/vol) MgSO 4 ·7H 2 O, 0.01% (wt/vol) yeast extract, 0.025% (wt/vol) glucose, and 0.1% (wt/vol) L-Pip (pH 7.0) and grown at 28°C with shaking. Escherichia coli JM109 and Rosetta2(DE3) (Novagen, WI, USA) were used as host strains for the overexpression of the recombinant enzymes and cultured at 28°C in LB medium, comprised of 1% (wt/v...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans -4-Hydroxylation of l -Pipecolic Acid

Hibi

Mori

Miyake

et al. 2016

Appl Environ Microbiol

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“…KCB13F003 was studied for the first time in search of potential new compounds through LC-MS screening. These investigations led to the discovery of two new cyclic depsipeptides and ulleungamides A and B [85]. Streptomyces sp.…”

Section: Dilemma Between the Knowledge From In Silico And The Vagaries Of In Vitro Methodsmentioning

confidence: 99%

In Silico/In Vitro Strategies Leading to the Discovery of New Nonribosomal Peptide and Polyketide Antibiotics Active against Human Pathogens

2021

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Antibiotics are majorly important molecules for human health. Following the golden age of antibiotic discovery, a period of decline ensued, characterised by the rediscovery of the same molecules. At the same time, new culture techniques and high-throughput sequencing enabled the discovery of new microorganisms that represent a potential source of interesting new antimicrobial substances to explore. The aim of this review is to present recently discovered nonribosomal peptide (NRP) and polyketide (PK) molecules with antimicrobial activity against human pathogens. We highlight the different in silico/in vitro strategies and approaches that led to their discovery. As a result of technological progress and a better understanding of the NRP and PK synthesis mechanisms, these new antibiotic compounds provide an additional option in human medical treatment and a potential way out of the impasse of antibiotic resistance.

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“…Two cyclic depsipeptides, ulleungamides A and B, were isolated from cultures of terrestrial Streptomyces sp. Ulleungamide A displayed growth inhibitory activity against Staphylococcus aureus and Salmonella typhimurium, without cytotoxicity (Son et al, 2015). (S)-2-isopropylsuccinic acid [41] was present in both ulleungamides.Two compounds, peptide-polyketide glycoside totopotensamide A and its aglycone totopotensamide B were isolated from Streptomyces sp.…”

Section: Branched Saturated and Unsaturated Fatty Acidsmentioning

confidence: 99%

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

Dembitsky¹

2017

Int. J. Curr. Res. Biosci. Plant Biol.

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A b s t r a c t A r t i c l e I n f oThis review is a comprehensive survey of unique, unusual, and rare fatty acids incorporated into natural marine and terrestrial peptides obtained from fungi, fungal endophytes, lichenized ascomycetes, basidiomycetes, and actinomycetes. Lots of fungal peptides display important biological activities of interest, which includes antitumor, antibacterial, antimicrobial, antifungal, phototoxic, HIV inhibitory, immunosuppressive properties, and other pharmacological activities. There is no doubt that they are of great importance, especially in medicinal chemistry and/or pharmaceutical application. This review presents structures of more than 150 fatty acids, incorporated into marine and terrestrial fungal lipopeptides.

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Ulleungamides A and B, Modified α,β-Dehydropipecolic Acid Containing Cyclic Depsipeptides from Streptomyces sp. KCB13F003

Cited by 29 publications

References 23 publications

Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans -4-Hydroxylation of l -Pipecolic Acid

Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans -4-Hydroxylation of l -Pipecolic Acid

In Silico/In Vitro Strategies Leading to the Discovery of New Nonribosomal Peptide and Polyketide Antibiotics Active against Human Pathogens

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

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