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Expanding the Described Metabolome of the Marine Cyanobacterium Moorea producens JHB through Orthogonal Natural Products Workflows.

Boudreau PD, Monroe EA, Mehrotra S, Desfor S, Korobeynikov A, Sherman DH, Murray TF, Gerwick L, Dorrestein PC, Gerwick WH - PLoS ONE (2015)

Bottom Line: In the current study, mass spectrometry-based 'molecular networking' was used to visualize the metabolome of Moorea producens JHB, and both guided and enhanced the isolation workflow, revealing additional metabolites in these compound classes.Further, we developed additional insight into the metabolic capabilities of this strain by genome sequencing analysis, which subsequently led to the isolation of a compound unrelated to the jamaicamide and hectochlorin families.Another approach involved stimulation of the biosynthesis of a minor jamaicamide metabolite by cultivation in modified media, and provided insights about the underlying biosynthetic machinery as well as preliminary structure-activity information within this structure class.

View Article: PubMed Central - PubMed

Affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, 92093, United States.

ABSTRACT
Moorea producens JHB, a Jamaican strain of tropical filamentous marine cyanobacteria, has been extensively studied by traditional natural products techniques. These previous bioassay and structure guided isolations led to the discovery of two exciting classes of natural products, hectochlorin (1) and jamaicamides A (2) and B (3). In the current study, mass spectrometry-based 'molecular networking' was used to visualize the metabolome of Moorea producens JHB, and both guided and enhanced the isolation workflow, revealing additional metabolites in these compound classes. Further, we developed additional insight into the metabolic capabilities of this strain by genome sequencing analysis, which subsequently led to the isolation of a compound unrelated to the jamaicamide and hectochlorin families. Another approach involved stimulation of the biosynthesis of a minor jamaicamide metabolite by cultivation in modified media, and provided insights about the underlying biosynthetic machinery as well as preliminary structure-activity information within this structure class. This study demonstrated that these orthogonal approaches are complementary and enrich secondary metabolomic coverage even in an extensively studied bacterial strain.

No MeSH data available.


Related in: MedlinePlus

TOCSY and key HMBC correlations in hectoramide (4).
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pone.0133297.g006: TOCSY and key HMBC correlations in hectoramide (4).

Mentions: The linkage of these residues was determined by 2D-NMR and MS2 fragmentation analysis. The N-methyl group of the first valine showed a correlation to the carbonyl of the second valine residue. In turn, this latter valine showed a correlation from its N-methyl to the carbonyl of the adjacent Mpla residue. As such, the initial structure proposed for this compound was (HOOC-N-Me-Val)-(N-Me-Val)-(Mpla-OH) (11); however, this was inconsistent with data from HRMS analysis. While the structure 11 would have a predicted molecular formula of C22H34N2O6, the MS1 [M+H]+ peak of this compound was at m/z 422.2648 Da, consistent with the molecular formula of C22H35N3O5. This was resolved by comparing predicted 13C-NMR shifts with various candidate structures, and indicated that a terminal primary amide and hydroxy group were fully consistent with the C-1 and C-14 13C-NMR shifts (Fig AT in S1 Text). In addition, MS2 fragmentation showed fragment ions diagnostic for this structure (Fig 6), explicitly (H2NOC-N-Me-Val)-(N-Me-Val)-(Mpla-OH).


Expanding the Described Metabolome of the Marine Cyanobacterium Moorea producens JHB through Orthogonal Natural Products Workflows.

Boudreau PD, Monroe EA, Mehrotra S, Desfor S, Korobeynikov A, Sherman DH, Murray TF, Gerwick L, Dorrestein PC, Gerwick WH - PLoS ONE (2015)

TOCSY and key HMBC correlations in hectoramide (4).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4519256&req=5

pone.0133297.g006: TOCSY and key HMBC correlations in hectoramide (4).
Mentions: The linkage of these residues was determined by 2D-NMR and MS2 fragmentation analysis. The N-methyl group of the first valine showed a correlation to the carbonyl of the second valine residue. In turn, this latter valine showed a correlation from its N-methyl to the carbonyl of the adjacent Mpla residue. As such, the initial structure proposed for this compound was (HOOC-N-Me-Val)-(N-Me-Val)-(Mpla-OH) (11); however, this was inconsistent with data from HRMS analysis. While the structure 11 would have a predicted molecular formula of C22H34N2O6, the MS1 [M+H]+ peak of this compound was at m/z 422.2648 Da, consistent with the molecular formula of C22H35N3O5. This was resolved by comparing predicted 13C-NMR shifts with various candidate structures, and indicated that a terminal primary amide and hydroxy group were fully consistent with the C-1 and C-14 13C-NMR shifts (Fig AT in S1 Text). In addition, MS2 fragmentation showed fragment ions diagnostic for this structure (Fig 6), explicitly (H2NOC-N-Me-Val)-(N-Me-Val)-(Mpla-OH).

Bottom Line: In the current study, mass spectrometry-based 'molecular networking' was used to visualize the metabolome of Moorea producens JHB, and both guided and enhanced the isolation workflow, revealing additional metabolites in these compound classes.Further, we developed additional insight into the metabolic capabilities of this strain by genome sequencing analysis, which subsequently led to the isolation of a compound unrelated to the jamaicamide and hectochlorin families.Another approach involved stimulation of the biosynthesis of a minor jamaicamide metabolite by cultivation in modified media, and provided insights about the underlying biosynthetic machinery as well as preliminary structure-activity information within this structure class.

View Article: PubMed Central - PubMed

Affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, 92093, United States.

ABSTRACT
Moorea producens JHB, a Jamaican strain of tropical filamentous marine cyanobacteria, has been extensively studied by traditional natural products techniques. These previous bioassay and structure guided isolations led to the discovery of two exciting classes of natural products, hectochlorin (1) and jamaicamides A (2) and B (3). In the current study, mass spectrometry-based 'molecular networking' was used to visualize the metabolome of Moorea producens JHB, and both guided and enhanced the isolation workflow, revealing additional metabolites in these compound classes. Further, we developed additional insight into the metabolic capabilities of this strain by genome sequencing analysis, which subsequently led to the isolation of a compound unrelated to the jamaicamide and hectochlorin families. Another approach involved stimulation of the biosynthesis of a minor jamaicamide metabolite by cultivation in modified media, and provided insights about the underlying biosynthetic machinery as well as preliminary structure-activity information within this structure class. This study demonstrated that these orthogonal approaches are complementary and enrich secondary metabolomic coverage even in an extensively studied bacterial strain.

No MeSH data available.


Related in: MedlinePlus