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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

The Potential Mechanisms of Halogenation of the Alkyne in Jamaicamide.
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pone.0133297.g008: The Potential Mechanisms of Halogenation of the Alkyne in Jamaicamide.

Mentions: Three mechanisms of bromination of 2 are conceivable using Br- by a nucleophilic halogenase, Br⦁ by a non-heme iron O2-dependent halogenase, or ‘Br+’ by a haloperoxidase or an FADH2-dependent halogenase (Fig 8) [47, 48]. Assuming bromination occurs on the terminal alkyne, as discussed above, then halogenation by a nucleophilic halogenase Br- is unlikely because this would putatively proceed through a high energy sp hybridized alkynyl carbocation species, which is highly disfavored over the resonance stabilized propargyl cation [49]. Bromination through the alkynyl radical is a conceivable mechanism, but the enzyme activity profile of reacting with both bromine and iodine and being unable to react with abundant chlorine is different from the reactivity profile of the known radical halogenases. Known non-heme iron O2-dependent halogenase can catalyze both chlorination and bromination (with chlorination being highly favored), and no reported iodination activity [48]; this may be due to the steric constraint of the larger iodide or because of a difference in fundamental energetics, radical iodination with elemental iodine is an endothermic process [49]. Bromination through a hypohalite ‘Br+’ species is compatible with the observation of an iodinated species and no chlorinated species because bromoperoxidases are capable of oxidizing the less electronegative iodine but not the more electronegative fluorine or chlorine [46]. Flavin-dependent halogenases have not been observed to iodinate, hypothesized as a problem of sterics for the larger iodide or hydrolysis of the bound iodine intermediate, so they are a poorer candidate for producing the reactive “X+” equivalent [48].


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)

The Potential Mechanisms of Halogenation of the Alkyne in Jamaicamide.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0133297.g008: The Potential Mechanisms of Halogenation of the Alkyne in Jamaicamide.
Mentions: Three mechanisms of bromination of 2 are conceivable using Br- by a nucleophilic halogenase, Br⦁ by a non-heme iron O2-dependent halogenase, or ‘Br+’ by a haloperoxidase or an FADH2-dependent halogenase (Fig 8) [47, 48]. Assuming bromination occurs on the terminal alkyne, as discussed above, then halogenation by a nucleophilic halogenase Br- is unlikely because this would putatively proceed through a high energy sp hybridized alkynyl carbocation species, which is highly disfavored over the resonance stabilized propargyl cation [49]. Bromination through the alkynyl radical is a conceivable mechanism, but the enzyme activity profile of reacting with both bromine and iodine and being unable to react with abundant chlorine is different from the reactivity profile of the known radical halogenases. Known non-heme iron O2-dependent halogenase can catalyze both chlorination and bromination (with chlorination being highly favored), and no reported iodination activity [48]; this may be due to the steric constraint of the larger iodide or because of a difference in fundamental energetics, radical iodination with elemental iodine is an endothermic process [49]. Bromination through a hypohalite ‘Br+’ species is compatible with the observation of an iodinated species and no chlorinated species because bromoperoxidases are capable of oxidizing the less electronegative iodine but not the more electronegative fluorine or chlorine [46]. Flavin-dependent halogenases have not been observed to iodinate, hypothesized as a problem of sterics for the larger iodide or hydrolysis of the bound iodine intermediate, so they are a poorer candidate for producing the reactive “X+” equivalent [48].

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