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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

Visualization of MS data with Molecular Networking.The process of forming a molecular network begins with collection of MS1 spectra (Step 1), from which parent ions are selected for MS2 fragmentation (Step 2). After the data is acquired it is processed by the Spectral Networking algorithm which converts MS2 data to vectors. The minimum number of peaks required to construct a vector is six; in this figure it is represented as only three so that the vector could be presented visually. It is important to note that when the multi-dimensional vectors are compared against all others by cosine function the vectors can have hundreds of dimensions (Step 3). This output is then visualized in Cytoscape with each node representing a MS2 spectrum labeled and colored based on its parent mass (Step 4).
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pone.0133297.g002: Visualization of MS data with Molecular Networking.The process of forming a molecular network begins with collection of MS1 spectra (Step 1), from which parent ions are selected for MS2 fragmentation (Step 2). After the data is acquired it is processed by the Spectral Networking algorithm which converts MS2 data to vectors. The minimum number of peaks required to construct a vector is six; in this figure it is represented as only three so that the vector could be presented visually. It is important to note that when the multi-dimensional vectors are compared against all others by cosine function the vectors can have hundreds of dimensions (Step 3). This output is then visualized in Cytoscape with each node representing a MS2 spectrum labeled and colored based on its parent mass (Step 4).

Mentions: Molecular networking utilizes MS2 data to sort parent ions based on their structural similarity. Secondary ion mass fragmentation data relate directly to molecular structure because chemical bonds break on the basis of bond strength, strain within a molecule, and ability of a fragment to stabilize charge [27]. Fragmentation patterns are thus intimately related to molecular structure, but independent of other bases for assessing compound similarity, such as the parent ion mass, halogen isotope pattern, or LCMS retention time. The Spectral Networking algorithm normalizes the intensity of fragment ions, uses each as an independent axis to construct a multidimensional vector for each spectrum, and finally compares the similarity of these vectors using a cosine function [27]. This cosine score is then used to plot the relationships between different parent ion masses with the open source software Cytoscape (Fig 2) [30].


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)

Visualization of MS data with Molecular Networking.The process of forming a molecular network begins with collection of MS1 spectra (Step 1), from which parent ions are selected for MS2 fragmentation (Step 2). After the data is acquired it is processed by the Spectral Networking algorithm which converts MS2 data to vectors. The minimum number of peaks required to construct a vector is six; in this figure it is represented as only three so that the vector could be presented visually. It is important to note that when the multi-dimensional vectors are compared against all others by cosine function the vectors can have hundreds of dimensions (Step 3). This output is then visualized in Cytoscape with each node representing a MS2 spectrum labeled and colored based on its parent mass (Step 4).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0133297.g002: Visualization of MS data with Molecular Networking.The process of forming a molecular network begins with collection of MS1 spectra (Step 1), from which parent ions are selected for MS2 fragmentation (Step 2). After the data is acquired it is processed by the Spectral Networking algorithm which converts MS2 data to vectors. The minimum number of peaks required to construct a vector is six; in this figure it is represented as only three so that the vector could be presented visually. It is important to note that when the multi-dimensional vectors are compared against all others by cosine function the vectors can have hundreds of dimensions (Step 3). This output is then visualized in Cytoscape with each node representing a MS2 spectrum labeled and colored based on its parent mass (Step 4).
Mentions: Molecular networking utilizes MS2 data to sort parent ions based on their structural similarity. Secondary ion mass fragmentation data relate directly to molecular structure because chemical bonds break on the basis of bond strength, strain within a molecule, and ability of a fragment to stabilize charge [27]. Fragmentation patterns are thus intimately related to molecular structure, but independent of other bases for assessing compound similarity, such as the parent ion mass, halogen isotope pattern, or LCMS retention time. The Spectral Networking algorithm normalizes the intensity of fragment ions, uses each as an independent axis to construct a multidimensional vector for each spectrum, and finally compares the similarity of these vectors using a cosine function [27]. This cosine score is then used to plot the relationships between different parent ion masses with the open source software Cytoscape (Fig 2) [30].

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