A butenolide intermediate in methylenomycin furan biosynthesis is implied by incorporation of stereospecifically 13C-labelled glycerols

Corre, Christophe; Haynes, Stuart W.; Malet, Nicolas; Song, Lijiang; Challis, Gregory L.

doi:10.1039/c000496k

Cited by 13 publications

(13 citation statements)

References 7 publications

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“…The biological function of AHFA 1 in the host cell is still unknown but is believed to be regulators of antibiotic biosynthesis in Streptomyces sp. RK44, analogous to the MMFs in S. coelicolor and GBLs in Streptomyces species [12,25]. Given the structural similarity of 1 with MMF4 [12], we predicted that 1 originated from an analogous biosynthetic pathway of MMF4.…”

Section: Proposed Mmf Biosynthetic Gene Cluster and Pathwaymentioning

confidence: 96%

“…Compound 1 was therefore identified as 2-alkyl-4-hydroxymethylfruan carboxamide (AHFA). MMFs share the common furan core in the structure, and the alkyl substituents at position C-2 of the ring can vary depending on which starter unit is incorporated during fatty acid biosynthesis [12,25]. Based on the HR ESIMS/GNPS analysis of the Streptomyces sp.…”

Section: Molecules 2020 25 460 3 Of 13mentioning

confidence: 99%

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Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Fang

Maglangit

et al. 2020

Molecules

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Streptomyces remains one of the prolific sources of structural diversity, and a reservoir to mine for novel natural products. Continued screening for new Streptomyces strains in our laboratory led to the isolation of Streptomyces sp. RK44 from the underexplored areas of Kintampo waterfalls, Ghana, Africa. Preliminary screening of the metabolites from this strain resulted in the characterization of a new 2-alkyl-4-hydroxymethylfuran carboxamide (AHFA) 1 together with five known compounds, cyclo-(L-Pro-Gly) 2, cyclo-(L-Pro-L-Phe) 3, cyclo-(L-Pro-L-Val) 4, cyclo-(L-Leu-Hyp) 5, and deferoxamine E 6. AHFA 1, a methylenomycin (MMF) homolog, exhibited anti-proliferative activity (EC50 = 89.6 µM) against melanoma A2058 cell lines. This activity, albeit weak is the first report amongst MMFs. Furthermore, the putative biosynthetic gene cluster (ahfa) was identified for the biosynthesis of AHFA 1. DFO-E 6 displayed potent anti-plasmodial activity (IC50 = 1.08 µM) against P. falciparum 3D7. High-resolution electrospray ionization mass spectrometry (HR ESIMS) and molecular network assisted the targeted-isolation process, and tentatively identified six AHFA analogues, 7–12 and six siderophores 13–18.

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Section: Proposed Mmf Biosynthetic Gene Cluster and Pathwaymentioning

confidence: 96%

Section: Molecules 2020 25 460 3 Of 13mentioning

confidence: 99%

Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Fang

Maglangit

et al. 2020

Molecules

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“…In terpenoids, furan ring biosynthesis utilizes active isoprene units, i.e., isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), as seen in the diterpenoids divinatorins (12) and bibifuran (13) [27,28]. The signaling molecules methylenomycin furans (MMFs) (14) and the furanylcarbonyl containing acyl rhamnosides (15) are formed by a mixed acetate-glycerol pathway [29][30][31][32]. The latter involves the condensation of a dihydroxyacetone-derived three-carbon unit originating from glycerol and a β-ketothioester intermediate derived from a polyketide synthase or fatty acid metabolism ( Figure 5).…”

Section: Putative Biosynthesis Of Peptides and 3-(3-furyl)-alaninementioning

confidence: 99%

The Rare Amino Acid Building Block 3-(3-furyl)-Alanine in the Formation of Non-ribosomal Peptides

Maddah

Nazir

König

2017

Natural Product Communications

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Microorganisms have made considerable contributions to the production of peptide secondary metabolites, many of them with therapeutic potential, e.g., the fungus-derived immunosuppressant cyclosporine A and the antibiotic daptomycin originating from Streptomyces. Most of the medically used peptides are the product of non-ribosomal peptide synthetases (NRPS), incorporating apart from proteinogenic also unique, non-proteinogenic amino acids into the peptides. An extremely rare such amino acid is 3-(3-furyl)-alanine. So far, only few peptides have been found that contain this residue, including the rhizonins, bingchamide B and endolides. The producer of the rhizonins was proven to be the bacterial endosymbiont Burkholderia endofungorum inside the fungus Rhizopus microsporus. The microbial origin, chemistry and bioactivity of the 3-(3-furyl)-alanine containing peptides are the focus of this review.

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“…25 The same precursors, dihydroxyacetone phosphate and b-ketoacyl CoA, were incorporated into both types of autoregulators. 26,27 Thus, g-butyrolactones and MMFs are biosynthesized by identical butenolide intermediates, followed by reduction of a double bond (g-butyrolactone) or recyclization of a butenolide ring (MMF) (Figure 3). The incorporation pattern of [U- 13 C] glycerol suggests that methylenomycin itself is also synthesized by a butenolide intermediate, which is formed by condensation of pentulose-5-phosphate with b-ketoacyl CoA (Figure 3).…”

Section: Biosynthesis Of Methylenomycin and Autoregulators In S Coelmentioning

confidence: 99%

Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters

Kinashi

2010

J Antibiot

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Many giant linear plasmids have been isolated from Streptomyces by using pulsed-field gel electrophoresis and some of them were found to carry an antibiotic biosynthetic cluster(s); SCP1 carries biosynthetic genes for methylenomycin, pSLA2-L for lankacidin and lankamycin, and pKSL for lasalocid and echinomycin. Accumulated data suggest that giant linear plasmids have played critical roles in genome evolution and horizontal transfer of secondary metabolism. In this review, I summarize typical examples of giant linear plasmids whose involvement in antibiotic production has been studied in some detail, emphasizing their finding processes and interaction with the host chromosomes. A hypothesis on horizontal transfer of secondary metabolism involving giant linear plasmids is proposed at the end.

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A butenolide intermediate in methylenomycin furan biosynthesis is implied by incorporation of stereospecifically 13C-labelled glycerols

Abstract: The label from [3-(13)C]-L-glycerol is incorporated into the hydroxymethyl group of methylenomycin furans suggesting a butenolide intermediate in their biosynthesis.

Cited by 13 publications

References 7 publications

Signalling and Bioactive Metabolites from Streptomyces sp. RK44

Signalling and Bioactive Metabolites from Streptomyces sp. RK44

The Rare Amino Acid Building Block 3-(3-furyl)-Alanine in the Formation of Non-ribosomal Peptides

Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters

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