Advances in linking polyketides and non-ribosomal peptides to their biosynthetic gene clusters in Fusarium

Nielsen, Mikkel Rank; Søndergaard, Teis Esben; Giese, Henriette; Sørensen, Jens Laurids

doi:10.1007/s00294-019-00998-4

Cited by 23 publications

(21 citation statements)

References 178 publications

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“…All PKS share different essential domains: acyltransferase domain (AT), β-ketosynthase domain (KS), β-ketoacyl reductase (KR), enoyl reductase (ER), methyl transferases (MT), thioesterases (TE), dehydrogenase (DH) and acyl carrier protein (ACP) domains. NRPS are composed by a variable number of modules, containing an adenylation (A), a peptide acyl-carrier (T), and a condensation (C) domain, plus different tailoring domains [96]. Finally, PKS-NRPS hybrid genes produce peptide-polyketide metabolites, in which polyketides are fused to an amino acid by an amide bond [97].…”

Section: Other Toxin-related Transcriptsmentioning

confidence: 99%

De novo Transcriptome of the Non-saxitoxin Producing Alexandrium tamutum Reveals New Insights on Harmful Dinoflagellates

et al. 2020

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Many dinoflagellates species, especially of the Alexandrium genus, produce a series of toxins with tremendous impacts on human and environmental health, and tourism economies. Alexandrium tamutum was discovered for the first time in the Gulf of Naples, and it is not known to produce saxitoxins. However, a clone of A. tamutum from the same Gulf showed copepod reproduction impairment and antiproliferative activity. In this study, the full transcriptome of the dinoflagellate A. tamutum is presented in both control and phosphate starvation conditions. RNA-seq approach was used for in silico identification of transcripts that can be involved in the synthesis of toxic compounds. Phosphate starvation was selected because it is known to induce toxin production for other Alexandrium spp. Results showed the presence of three transcripts related to saxitoxin synthesis (sxtA, sxtG and sxtU), and others potentially related to the synthesis of additional toxic compounds (e.g., 44 transcripts annotated as “polyketide synthase”). These data suggest that even if this A. tamutum clone does not produce saxitoxins, it has the potential to produce toxic metabolites, in line with the previously observed activity. These data give new insights into toxic microalgae, toxin production and their potential applications for the treatment of human pathologies.

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Section: Other Toxin-related Transcriptsmentioning

confidence: 99%

De novo Transcriptome of the Non-saxitoxin Producing Alexandrium tamutum Reveals New Insights on Harmful Dinoflagellates

et al. 2020

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“…A broader study containing a plethora of other pathways from different origins would indicate whether this is a universally optimal PPTase partner or if it is only highly efficient when working with the Fusarium PKSs, as in this study. In this regard, it is worth noticing that F. verticillioides also contains the functional Fsr-gene cluster homologous to the fsr-genes expressed in the bostrycoidin pathway [ 43 , 44 ], and therefore has followed the same evolutionary path.…”

Section: Resultsmentioning

confidence: 99%

Speed dating for enzymes! Finding the perfect phosphopantetheinyl transferase partner for your polyketide synthase

et al. 2022

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The biosynthetic pathways for the fungal polyketides bikaverin and bostrycoidin, from Fusarium verticillioides and Fusarium solani respectively, were reconstructed and heterologously expressed in S. cerevisiae alongside seven different phosphopantetheinyl transferases (PPTases) from a variety of origins spanning bacterial, yeast and fungal origins. In order to gauge the efficiency of the interaction between the ACP-domains of the polyketide synthases (PKS) and PPTases, each were co-expressed individually and the resulting production of target polyketides were determined after 48 h of growth. In co-expression with both biosynthetic pathways, the PPTase from Fusarium verticillioides (FvPPT1) proved most efficient at producing both bikaverin and bostrycoidin, at 1.4 mg/L and 5.9 mg/L respectively. Furthermore, the remaining PPTases showed the ability to interact with both PKS’s, except for a single PKS-PPTase combination. The results indicate that it is possible to boost the production of a target polyketide, simply by utilizing a more optimal PPTase partner, instead of the commonly used PPTases; NpgA, Gsp and Sfp, from Aspergillus nidulans, Brevibacillus brevis and Bacillus subtilis respectively.

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“…So far, the only secondary metabolite to be linked to a gene directly in F. solani is sansalvamide [21]. However, comparative analyses have revealed that F. solani contain numerous biosynthetic gene clusters, including 13 polyketide synthases ( PKSs ) of which only three can be linked to a product based on orthology [12–14, 16, 17, 44]. The pSHUT4- eYFP vector can be modified and used to overexpress local transcription factors of biosynthetic gene clusters, which has proven a highly successful approach to identify novel secondary metabolites [45].…”

Section: Resultsmentioning

confidence: 99%

“…Several bioactive secondary metabolites have been identified in FSSC, including cyclosporin, gibepyrone A, lucilactaene, sansalvamide and the pigments fusarubin, javanicin and bostrycoidin [11]. Analyses of the genome of the first sequenced FSSC strain (77-13-4; FGSC 9596) revealed the presence of 13 polyketide synthases ( PKSs ) and 13 non-ribosomal peptide synthetases ( NRPSs ) [2] and subsequent orthology studies have linked fusarubin, javanicin, bostrycoidin ( PKS3 ; fsr ), gibepyrone A ( PKS8, Gpy1 ), lucilactaene ( PKS10 ) to their responsible gene clusters [12–17].…”

Section: Introductionmentioning

confidence: 99%

A new vector system for targeted integration and overexpression of genes in the crop pathogen Fusarium solani

Nielsen

Holzwarth

Brew

et al. 2019

Fungal Biol Biotechnol

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BackgroundBesides their ability to produce several interesting bioactive secondary metabolites, members of the Fusarium solani species complex comprise important pathogens of plants and humans. One of the major obstacles in understanding the biology of this species complex is the lack of efficient molecular tools for genetic manipulation.ResultsTo remove this obstacle we here report the development of a reliable system where the vectors are generated through yeast recombinational cloning and inserted into a specific site in F. solani through Agrobacterium tumefaciens-mediated transformation. As proof-of-concept, the enhanced yellow fluorescent protein (eYFP) was inserted in a non-coding genomic position of F. solani and subsequent analyses showed that the resulting transformants were fluorescent on all tested media. In addition, we cloned and overexpressed the Zn(II)2Cys6 transcriptional factor fsr6 controlling mycelial pigmentation. A transformant displayed deep red/purple pigmentation stemming from bostrycoidin and javanicin.ConclusionBy creating streamlined plasmid construction and fungal transformation systems, we are now able to express genes in the crop pathogen F. solani in a reliable and fast manner. As a case study, we targeted and activated the fusarubin (PKS3: fsr) gene cluster, which is the first case study of secondary metabolites being directly associated with the responsible gene cluster in F. solani via targeted activation. The system provides an approach that in the future can be used by the community to understand the biochemistry and genetics of the Fusarium solani species complex, and is obtainable from Addgene catalog #133094.Graphic abstract

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Advances in linking polyketides and non-ribosomal peptides to their biosynthetic gene clusters in Fusarium

Cited by 23 publications

References 178 publications

De novo Transcriptome of the Non-saxitoxin Producing Alexandrium tamutum Reveals New Insights on Harmful Dinoflagellates

De novo Transcriptome of the Non-saxitoxin Producing Alexandrium tamutum Reveals New Insights on Harmful Dinoflagellates

Speed dating for enzymes! Finding the perfect phosphopantetheinyl transferase partner for your polyketide synthase

A new vector system for targeted integration and overexpression of genes in the crop pathogen Fusarium solani

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