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. 2015 Sep 14;54(38):11063-7.
doi: 10.1002/anie.201503186. Epub 2015 Jul 31.

Biosynthesis-assisted structural elucidation of the bartolosides, chlorinated aromatic glycolipids from cyanobacteria

Affiliations

Biosynthesis-assisted structural elucidation of the bartolosides, chlorinated aromatic glycolipids from cyanobacteria

Pedro N Leão et al. Angew Chem Int Ed Engl. .

Erratum in

Abstract

The isolation of the bartolosides, unprecedented cyanobacterial glycolipids featuring aliphatic chains with chlorine substituents and C-glycosyl moieties, is reported. Their chlorinated dialkylresorcinol (DAR) core presented a major structural-elucidation challenge. To overcome this, we discovered the bartoloside (brt) biosynthetic gene cluster and linked it to the natural products through in vitro characterization of the DAR-forming ketosynthase and aromatase. Bioinformatic analysis also revealed a novel potential halogenase. Knowledge of the bartoloside biosynthesis constrained the DAR core structure by defining key pathway intermediates, ultimately allowing us to determine the full structures of the bartolosides. This work illustrates the power of genomics to enable the use of biosynthetic information for structure elucidation.

Keywords: biosynthesis; cyanobacteria; dialkylresorcinol; glycolipids; structure elucidation.

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Figures

Figure 1
Figure 1
The bartolosides are chlorinated aromatic glycolipids found in cyanobacteria belonging to different genera. Optical photomicrographs of the producing organisms and structures of: a) bartoloside A (1) and b) bartolosides B, C, and D (24). Scale bar: 10 μm.
Figure 2
Figure 2
NMR-derived structural information for 2. a) Fragments obtained from 1D and 2D NMR spectroscopy, with key HMBC correlations highlighted. b) 1D TOCSY experiments with irradiation of the benzylic protons on each chain reveal propagation up to methylene groups vicinal to the chlorinated methine moieties.
Figure 3
Figure 3
Biosynthesis of the bartolosides. a) Organization of the brt gene cluster from S. salina LEGE 06155 and annotated gene functions. b) Proposal for the biosynthesis of the dialkylresorcinol scaffold found in 24.
Figure 4
Figure 4
BrtD and BrtC synthesize the DAR core of bartoloside B. a) Schematic representation of the N-His6-tagged BrtD and BrtC coupled assay. b) LC-HR-ESI-MS derived extracted ion chromatograms (EICs) showing diketone production by N-His6-BrtD and DAR production by N-His6-BrtC. All chromatograms have the same scale. c) HR-MS2 characterization of the reaction products 5, 6, and 7 (dashed lines represent ions generated by a fragmentation on an alkyl chain).
Figure 5
Figure 5
NMR-based (HSQC-TOCSY, 600 MHz and HMBC, 400 MHz) deduction of the position of the Cl atoms in each chain in 2. a) Proposed positioning and key HMBC and HSQC-TOCSY correlations leading to the structural assignment. b) HSQC-TOCSY spectrum of 2, highlighting the spectral deconvolution leading to the assignment of the methylene group resonating at δ=1.31 ppm in the C15 chain. c) Key HSQC-TOCSY correlations (circles) connecting the benzylic position to the chlorinated position in the C15 chain. d) Assignment of the bridging methylene group in the C12 chain by HSQC-TOCSY analysis (key correlation circled). e) HMBC data highlighting the correlation (circled) from a pair of diastereotopic protons (vicinal to the chlorinated position) to the ω-3 methylene carbon atom.

References

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