Isolation of Isotrichophycin C and Trichophycins G–I from a Collection of Trichodesmium thiebautii

Abstract

The trichophycin family of compounds are chlorinated polyketides first discovered from environmental collections of a bloom-forming Trichodesmium sp. cyanobacterium. In an effort to fully capture the chemical space of this group of metabolites, the utilization of MS/MS-based molecular networking of a Trichodesmium thiebautii extract revealed a metabolome replete with halogenated compounds. Subsequent MS-guided isolation resulted in the characterization of isotrichophycin C and trichophycins G-I (1-4). These new metabolites had intriguing structural variations from those trichophycins previously characterized, which allowed for a comparative study to examine structural features that are associated with toxicity to murine neuroblastoma cells. Additionally, we propose the absolute configuration of the previously characterized trichophycin A (5). Overall, the metabolome of the Trichodesmium bloom is hallmarked by an unprecedented amount of chlorinated molecules, many of which remain to be structurally characterized. 4 and derivatives of 1, 3, and trichophycin A. ECD data of 1 and trichophycin C. EC50 curves of 1-3 and acetylated derivatives, and phylogenetic analysis.

Marine natural products

“…Subsequent MS-guided isolation resulted in the identification of isotrichophycin C 284 and trichophycins G–I 285–287 . 113 The first application of an NMR-based machine learning tool named “Small Molecule Accurate Recognition Technology” (SMART 2.0) for mixture analysis and subsequent accelerated discovery of new MNPs was reported. This strategy was applied to a cytotoxic Symploca sp.…”

Spatial and Temporal Resolution of Cyanobacterial Bloom Chemistry Reveals an Open-OceanTrichodesmium thiebautiias a Talented Producer of Specialized Metabolites

“…Additionally, we identified key genetic architecture in the T. thiebautii H94 genome that is consistent with the generation of key functional groups in many of the metabolites we have characterized, i.e., the chlorovinylidene group and terminal vinyl chloride present in the trichophycins and smenolactones, the trichotoxins, the smenamides, the conulothiazoles, and trichothiazole A. [19–21,23–30] This study provokes intriguing questions with respect to the full chemical potential of the members of this genus, and the potential for the development of metabologenomics approaches for the species in this group of ecologically important organisms.…”

“…an initial collection of Trichodesmium thiebautii biomass near North Padre Island, TX in 2014 provided the first evidence that there was a Trichodesmium species capable of prolific specialized metabolite production in the GoM. Mining this biomass resulted in the characterization of 24 new molecules, [20][21][22][23]26,29,30] including 1 presented in the current report.…”

Obligate Brominating Enzymes Underlie Bromoform Production by Marine Cyanobacteria

“…2018, McManus et al. 2020). A homology search reveals that marine filamentous bacteria of genera Symploca , Leptolyngbya , Okeania , and Moorea , among others, all possess VHPOs with as yet unidentified halide specificities and physiological roles.…”