Identification, cloning, expression and functional interrogation of the biosynthetic pathway of the polychlorinated triphenyls ambigol A–C from<i>Fischerella ambigua</i>108b

Duell, Elke R.; Milzarek, Tobias M.; Omari, Mustafa El; Linares-Otoya, Luis; Schäberle, Till F.; König, Gabriele M.; Gulder, Tobias A. M.

doi:10.1039/d0qo00707b

Cited by 15 publications

(23 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using mock community data, Pérez et al demonstrated that full-sized BGCs could be successfully recovered from long-read metagenomic sequencing [11]. In light of recent advances in PCR-based cloning techniques that comprise heterologous expression of BGCs based on PCR amplification [12][13][14][15], the recovery of full-length metagenomic BGC sequences is promising as these sequences would be amenable to PCR amplification.…”

Section: Introductionmentioning

confidence: 99%

Biosynthetic potential of uncultured Antarctic soil bacteria revealed through long-read metagenomic sequencing

et al. 2021

View full text Add to dashboard Cite

The growing problem of antibiotic resistance has led to the exploration of uncultured bacteria as potential sources of new antimicrobials. PCR amplicon analyses and short-read sequencing studies of samples from different environments have reported evidence of high biosynthetic gene cluster (BGC) diversity in metagenomes, indicating their potential for producing novel and useful compounds. However, recovering full-length BGC sequences from uncultivated bacteria remains a challenge due to the technological restraints of short-read sequencing, thus making assessment of BGC diversity difficult. Here, long-read sequencing and genome mining were used to recover >1400 mostly full-length BGCs that demonstrate the rich diversity of BGCs from uncultivated lineages present in soil from Mars Oasis, Antarctica. A large number of highly divergent BGCs were not only found in the phyla Acidobacteriota, Verrucomicrobiota and Gemmatimonadota but also in the actinobacterial classes Acidimicrobiia and Thermoleophilia and the gammaproteobacterial order UBA7966. The latter furthermore contained a potential novel family of RiPPs. Our findings underline the biosynthetic potential of underexplored phyla as well as unexplored lineages within seemingly well-studied producer phyla. They also showcase long-read metagenomic sequencing as a promising way to access the untapped genetic reservoir of specialised metabolite gene clusters of the uncultured majority of microbes.

show abstract

Section: Introductionmentioning

confidence: 99%

Biosynthetic potential of uncultured Antarctic soil bacteria revealed through long-read metagenomic sequencing

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The ambigols are polyhalogenated triphenols that are composed of dechlorinated phenol building blocks are linked by biaryl or biaryl ether bonds. While they are structurally related to the polybrominated diphenyls recently reported from marine cyanobacteria [ 52 , 53 ], they remain biosynthetically unrelated [ 17 ]. Furthermore, the ambigols were reported to possess a range of bioactivities including antifungal, antibacterial and molluscicidal, as well as having been implicated in the increase of the quorum-sensing regulated red pigment prodigiosin.…”

Section: Discussionmentioning

confidence: 99%

“…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 ].…”

Section: Discussionmentioning

confidence: 99%

“…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 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2021

View full text Add to dashboard Cite

Since 1965 a cyanobacterial strain termed ‘Fischerella ambigua 108b’ was the object of several studies investigating its potential as a resource for new bioactive compounds in several European institutes. Over decades these investigations uncovered several unique small molecules and their respective biosynthetic pathways, including the polychlorinated triphenyls of the ambigol family and the tjipanazoles. However, the true taxonomic character of the producing strain remained concealed until now. Applying a polyphasic approach considering the phylogenetic position based on the 16S rRNA and the protein coding gene rbcLX, secondary structures and morphological features, we present the strain ‘Fischerella ambigua 108b’ as Symphyonema bifilamentata sp. nov. 97.28. Although there is the type species (holotype) S. sinense C.-C. Jao 1944 there is no authentic living strain or material for genetic analyses for the genus Symphyonema available. Thus we suggest and provide an epitypification of S. bifilamentata sp. nov. 97.28 as a valid reference for the genus Symphyonema. Its affiliation to the family Symphyonemataceae sheds not only new light on this rare taxon but also on the classes of bioactive metabolites of these heterocytous and true-branching cyanobacteria which we report here. We show conclusively that the literature on the isolation of bioactive products from this organism provides further support for a clear distinction between the secondary metabolism of Symphyonema bifilamentata sp. nov. 97.28 compared to related and other taxa, pointing to the assignment of this organism into a separate genus.

show abstract

“…5 Direct Pathway Cloning (DiPaC) is a recently developed strategy for BGC capture and heterologous expression that has shown promise in the expression of cyanobacterial BGCs, including complex polyketide synthase (PKS)/non-ribosomal peptide synthetase (NRPS) pathways. [5][6][7][8][9] Microginins are a large group of over 80 cyanobacterial secondary metabolites. 10 Their structures can be summarized as linear lipopeptides featuruing a 3-amino fatty acyl residue connected to a peptide (typically three or four amino acid residues).…”

Section: Introductionmentioning

confidence: 99%

Discovery and heterologous expression of microginins from Microcystis aeruginosa LEGE 91341

Eusébio

Castelo-Branco

Sousa

et al. 2022

Preprint

View full text Add to dashboard Cite

Microginins are a large family of cyanobacterial lipopeptide protease inhibitors. A hybrid polyketide synthase (PKS)/non-ribosomoal peptide synthetase (NRPS) biosynthetic gene cluster (BGC) found in several microginin-producing strains – mic – was proposed to encode the production of microginins, based on bioinformatic analysis. Here, we explored a cyanobacte-rium, Microcystis aeruginosa LEGE 91341, which contains a mic BGC, to discover twelve new microginin variants. The new compounds contain uncommon amino acids, namely homophenylalanine (Hphe), homotyrosine (Htyr) or methylproline, as well as a 3-aminodecanoic acid (Ada) residue, which in some variants was chlorinated at its terminal methyl group. We have used Direct Pathway Cloning (DiPaC) to heterologously express the mic BGC from M. aeruginosa LEGE 91341 in E. coli, which led to the production of several microginins. This proved that the mic BGC is, in fact, responsible for the biosynthesis of microginins and paves the way to accessing new variants from (meta)genome data or through pathway engineering.

show abstract

Identification, cloning, expression and functional interrogation of the biosynthetic pathway of the polychlorinated triphenyls ambigol A–C fromFischerella ambigua108b

Abstract: The terrestrial cyanobacterium Fischerella ambigua 108b produces the three polychlorinated triphenyls ambigol A–C that exhibit interesting antimicrobial, antiviral and cytotoxic activities. They are structurally related to polybrominated diphenylethers synthesized by...

Cited by 15 publications

References 51 publications

Biosynthetic potential of uncultured Antarctic soil bacteria revealed through long-read metagenomic sequencing

Biosynthetic potential of uncultured Antarctic soil bacteria revealed through long-read metagenomic sequencing

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

Discovery and heterologous expression of microginins from Microcystis aeruginosa LEGE 91341

Contact Info

Product

Resources

About