Halogenation‐Guided Chemical Screening Provides Insight into Tjipanazole Biosynthesis by the Cyanobacterium Fischerella ambigua

Abstract

Halogenated natural products (HNPs) show a wide range of interesting biological activities. Chemistry‐guided screening with a software tool dedicated to identifying halogenated compounds in HPLC‐MS data indicated the presence of several uncharacterised HNPs in an extract of the cyanobacterium Fischerella ambigua (Näg.) Gomont 108b. Three new natural products, tjipanazoles K, L, and M, were isolated from this strain together with the known tjipanazoles D and I. Taking into account the structures of all tjipanazole derivatives detected in this strain, reanalysis of the tjipanazole biosynthetic gene cluster allowed us to propose a biosynthetic pathway for the tjipanazoles. As the isolated tjipanazoles show structural similarity to arcyriaflavin A, an inhibitor of the clinically relevant multidrug‐transporter ABCG2 overexpressed by different cancer cell lines, the isolated compounds were tested for ABCG2 inhibitory activity. Only tjipanazole K showed appreciable transporter inhibition, whereas the compounds lacking the pyrrolo[3,4‐c] ring or featuring additional chloro substituents were found to be much less active.

Symphyonema bifilamentata sp. nov., the Right Fischerella ambigua 108b: Half a Decade of Research on Taxonomy and Bioactive Compounds in New Light

“…Since the initial discovery of the ambigols and tjipanazoles, these molecules have not been discovered in any other Fischerella strain. The biosynthetic gene cluster for both the ambigols ( ab ) and tjipanazoles ( tjp ) were recently characterised by Duell et al, [ 17 ] and Chilczuk et al, [ 18 ], respectively. To determine if other organisms may have the genetic capability to produce these molecules, we performed a bioinformatic screening across all genomes within the NCBI database using cblaster [ 56 ].…”

“…From that point forward, ‘ Fischerella ambigua 108b’ was the subject of various studies on bioactive cyanobacterial products without confirmation of its taxonomic assignment. Between 1965 and 2020 several studies were conducted that led, among other things, to the discovery of the polychlorinated triphenyls ambigol A–E [ 14 , 15 , 16 ] and their biosynthetic pathway [ 17 ], and the isolation of the tjipanazoles and characterization of their biosynthesis [ 18 ]. These and other findings were always discussed in light of bioactive compounds and their metabolic pathways extracted from related species, such as F. thermalis or F. muscicola , or related genera, including Westiellopsis , Hapalosiphon or Nostochopsis .…”

Nontargeted LC/ESI-HRMS Detection of Polyhalogenated Compounds in Marine Mammals Stranded on French Atlantic Coasts

“…Then, the objective was to characterize in these samples amenable non-conventional and known polyhalogenated organic compounds, using a recently made publicly available open-source software, HaloSeeker 1.0, for annotating chemical formulas and select signals worth further investigation. 26,27 The perspective is to enlarge the knowledge of the HOC exposome. EXPERIMENTAL A glossary of selected terms, abbreviations and chemicals is available in the Supporting Information.…”

“…Because several biological (e.g., age and sex) and ecological factors (e.g., trophic level and prey type) affect the pollutant burden in marine mammals, − species with different feeding strategies (e.g., consumers of fish vs cephalopods) and habitats (e.g., inshore vs offshore) were selected, meaning different environmental pollution exposures. Then, the objective was to characterize in these samples amenable nonconventional and known polyhalogenated organic compounds, using open-source software recently made publicly available, HaloSeeker 1.0, for annotating chemical formulas and select signals worth further investigation. , The goal is to improve our knowledge of the HOC exposome.…”

“…Then, the objective was to characterize in these samples amenable nonconventional and known polyhalogenated organic compounds, using opensource software recently made publicly available, HaloSeeker 1.0, for annotating chemical formulas and select signals worth further investigation. 26,27 The goal is to improve our knowledge of the HOC exposome.…”