Putative Biosynthesis of Talarodioxadione &amp; Talarooxime from Talaromyces stipitatus

Fahad, Ahmed J Al

doi:10.3390/molecules27144473

“…The production of beneficial biotechnological metabolites by the T. pinophilus isolate in this study can be linked to the putative biosynthetic gene cluster previously reported in some fungal isolates, including the genera Talaromyces [ 6 , 49 ]. A comparative genomic analysis of T. pinophilus 1–95 revealed that the fungal strain contained 68 metabolism gene clusters containing 401 putative genes, including Type1 polyketide synthase genes and nonribosomal peptide synthase genes [ 6 ].…”

Section: Discussionsupporting

confidence: 65%

“…The authors found that T. pinophilus 1–95 contains more secondary metabolites than other related filamentous fungi, promoting the cultivation of T. pinophilus for the high synthesis of beneficial metabolites. In addition, Ahmed [ 49 ] complete genome sequence of T. stipitatus and the advancement in bioinformatics tools have facilitated the discovery of the fungus’s biosynthetic potential, with the identification of a putative biosynthetic gene cluster (BGC) of the polyesters encoding a highly reducing polyketide synthase (HR-PKS) and nonreducing polyketide synthase (NR-PKS). According to Le Govic et al [ 50 ], these genes are responsible for forming several metabolites in bacterial and fungal species.…”

Section: Discussionmentioning

confidence: 99%

Variability in metabolites produced by Talaromyces pinophilus SPJ22 cultured on different substrates

Adelusi

¹

,

Gbashi

²

,

Adebiyi

³

et al. 2022

Fungal Biol Biotechnol

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Background Several metabolites released by fungal species are an essential source of biologically active natural substances. Gas chromatography high resolution time-of-flight mass spectrometry (GC-HRTOF-MS) is one of the techniques used in profiling the metabolites produced by microorganisms, including Talaromyces pinophilus. However, there is limited information regarding differential substrates’ impacts on this fungal strain’s metabolite profiling. This study examined the metabolite profile of T. pinophilus strain SPJ22 cultured on three different media, including solid czapek yeast extract agar (CYA), malt extract agar (MEA) and potato dextrose agar (PDA) using GC-HRTOF-MS. The mycelia including the media were plugged and dissolved in 5 different organic solvents with varying polarities viz.: acetonitrile, dichloromethane, hexane, 80% methanol and water, and extracts analysed on GC-HRTOF-MS. Results The study revealed the presence of different classes of metabolites, such as fatty acids (2.13%), amides (4.26%), alkanes (34.04%), furan (2.13%), ketones (4.26%), alcohols (14.89%), aromatic compounds (6.38%), and other miscellaneous compounds (17.02%). Significant metabolites such as acetic acid, 9-octadecenamide, undecanoic acid methyl ester, hydrazine, hexadecane, nonadecane, eicosane, and other compounds reported in this study have been widely documented to have plant growth promoting, antimicrobial, anti-inflammatory, antioxidant, and biofuel properties. Furthermore, T. pinophilus grown on PDA and MEA produced more than twice as many compounds as that grown on CYA. Conclusion Thus, our result showed that the production of essential metabolites from T. pinophilus is substrate dependent, with many of these metabolites known to have beneficial characteristics, and as such, this organism can be utilised as a sustainable and natural source for these useful organic molecules.

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“…Additional domain dissection experiments, including the use of 1 loaded to purified ACP Preu6 , are under way in our labs to gain a full mechanistic understanding of this intricate dimerization process and the exact nature of the SAT‐TE collaboration. In the meantime, investigations of direct SAT‐TE interactions in other fungal nrPKS systems forming oligomeric products such as the polylactone synthases may also be considered [20, 21] …”

Section: Figurementioning

confidence: 99%

Didepside Formation by the Nonreducing Polyketide Synthase Preu6 of Preussia isomera Requires Interaction of Starter Acyl Transferase and Thioesterase Domains

Liu

¹

,

Zhang

²

,

Gao

³

et al. 2022

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Orsellinic acid (OA) derivatives are produced by filamentous fungi using nonreducing polyketide synthases (nrPKSs). The chain-releasing thioesterase (TE) domains of such nrPKSs were proposed to also catalyze dimerization to yield didepsides, such as lecanoric acid. Here, we use combinatorial domain exchanges, domain dissections and reconstitutions to reveal that the TE domain of the lecanoric acid synthase Preu6 of Preussia isomera must collaborate with the starter acyl transferase (SAT) domain from the same nrPKS. We show that artificial SAT-TE fusion proteins are highly effective catalysts and reprogram the ketide homologation chassis to form didepsides. We also demonstrate that dissected SAT and TE domains of Preu6 physically interact, and SAT and TE domains of OA-synthesizing nrPKSs may co-evolve. Our work highlights an unexpected domain-domain interaction in nrPKSs that must be considered for the combinatorial biosynthesis of unnatural didepsides, depsidones, and diphenyl ethers.Derivatives of orsellinic acid (OA, 1) form a large class of structurally diverse polyketides widely distributed in plants, lichens, algae, fungi and bacteria. [1] OA polymers, that is, depsides, depsidones, and diphenyl ethers, feature ester or ether linkages. [2,3] These linkages may form by oxidative coupling or oxidative rearrangements catalyzed by tailoring enzymes after the release of the polyketide core from the nonreducing polyketide synthase (nrPKS) enzyme. [4][5][6] Alter-natively, such linkages result from nrPKS-catalyzed transformations of nascent, acyl carrier protein-bound intermediates. [7,8] Among the ester-linked OA dimers, lecanoric acid (2), a lichen metabolite also produced by filamentous fungi, displays various biological activities, including histidine decarboxylase inhibitory, [9] radical scavenging, [10,11] and antifungal activities. [12] Three nrPKSs from different fungi have been shown to yield the didepside 2, all without the involvement of post-PKS tailoring enzymes. These nrPKSs (AN7909 from Aspergillus nidulans, [7,8] CPUR_07425 from Claviceps purpurea, [13] and Preu6 from Preussia isomera, [12] ) share the same domain architecture, that is, SAT (starter acyl transferase)-KS (ketoacyl synthase)-AT (acyl transferase)-PT (product template)-ACP1 and 2 (acyl carrier protein 1 and 2)-TE (thioesterase) (Figure S1, Table S1).When expressed in Saccharomyces cerevisiae, AN7909 affords the diaryl ether diorcinolic acid (3) with only trace amounts of 2. [7,8] The dissected AN7909-TE efficiently converts the N-acetylcysteamine thioester of 2 (2-SNAC) into 3 and 1-SNAC into 1 in vitro (Figure 1A). [8] This confirms that AN7909-TE not only releases both 3 and 1, but also catalyzes a Smiles rearrangement to the diaryl ether 3. [8] However, AN7909-TE converts 1-SNAC into 3 with low efficiency in vitro; [8] therefore, its role in the in vivo formation of the ester 2 remains to be further elucidated.In contrast, overexpression of CPUR_07425 in C. purpurea yielded 2 and its ethyl ester, with only trace amounts of diaryl et...

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“…In the meantime, investigations of direct SAT-TE interactions in other fungal nrPKS systems forming oligomeric products such as the polylactone synthases may also be considered. [20,21]…”

Section: Angewandte Chemiementioning

confidence: 99%

Didepside Formation by the Nonreducing Polyketide Synthase Preu6 of Preussia isomera Requires Interaction of Starter Acyl Transferase and Thioesterase Domains

Liu

¹

,

Zhang

²

,

Gao

³

et al. 2022

View full text Add to dashboard Cite

Orsellinic acid (OA) derivatives are produced by filamentous fungi using nonreducing polyketide synthases (nrPKSs). The chain-releasing thioesterase (TE) domains of such nrPKSs were proposed to also catalyze dimerization to yield didepsides, such as lecanoric acid. Here, we use combinatorial domain exchanges, domain dissections and reconstitutions to reveal that the TE domain of the lecanoric acid synthase Preu6 of Preussia isomera must collaborate with the starter acyl transferase (SAT) domain from the same nrPKS. We show that artificial SAT-TE fusion proteins are highly effective catalysts and reprogram the ketide homologation chassis to form didepsides. We also demonstrate that dissected SAT and TE domains of Preu6 physically interact, and SAT and TE domains of OA-synthesizing nrPKSs may co-evolve. Our work highlights an unexpected domain-domain interaction in nrPKSs that must be considered for the combinatorial biosynthesis of unnatural didepsides, depsidones, and diphenyl ethers.Derivatives of orsellinic acid (OA, 1) form a large class of structurally diverse polyketides widely distributed in plants, lichens, algae, fungi and bacteria. [1] OA polymers, that is, depsides, depsidones, and diphenyl ethers, feature ester or ether linkages. [2,3] These linkages may form by oxidative coupling or oxidative rearrangements catalyzed by tailoring enzymes after the release of the polyketide core from the nonreducing polyketide synthase (nrPKS) enzyme. [4][5][6] Alter-natively, such linkages result from nrPKS-catalyzed transformations of nascent, acyl carrier protein-bound intermediates. [7,8] Among the ester-linked OA dimers, lecanoric acid (2), a lichen metabolite also produced by filamentous fungi, displays various biological activities, including histidine decarboxylase inhibitory, [9] radical scavenging, [10,11] and antifungal activities. [12] Three nrPKSs from different fungi have been shown to yield the didepside 2, all without the involvement of post-PKS tailoring enzymes. These nrPKSs (AN7909 from Aspergillus nidulans, [7,8] CPUR_07425 from Claviceps purpurea, [13] and Preu6 from Preussia isomera, [12] ) share the same domain architecture, that is, SAT (starter acyl transferase)-KS (ketoacyl synthase)-AT (acyl transferase)-PT (product template)-ACP1 and 2 (acyl carrier protein 1 and 2)-TE (thioesterase) (Figure S1, Table S1).When expressed in Saccharomyces cerevisiae, AN7909 affords the diaryl ether diorcinolic acid (3) with only trace amounts of 2. [7,8] The dissected AN7909-TE efficiently converts the N-acetylcysteamine thioester of 2 (2-SNAC) into 3 and 1-SNAC into 1 in vitro (Figure 1A). [8] This confirms that AN7909-TE not only releases both 3 and 1, but also catalyzes a Smiles rearrangement to the diaryl ether 3. [8] However, AN7909-TE converts 1-SNAC into 3 with low efficiency in vitro; [8] therefore, its role in the in vivo formation of the ester 2 remains to be further elucidated.In contrast, overexpression of CPUR_07425 in C. purpurea yielded 2 and its ethyl ester, with only trace amounts of diaryl et...

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Putative Biosynthesis of Talarodioxadione & Talarooxime from Talaromyces stipitatus

Cited by 3 publications

References 49 publications

Variability in metabolites produced by Talaromyces pinophilus SPJ22 cultured on different substrates

Variability in metabolites produced by Talaromyces pinophilus SPJ22 cultured on different substrates

Didepside Formation by the Nonreducing Polyketide Synthase Preu6 of Preussia isomera Requires Interaction of Starter Acyl Transferase and Thioesterase Domains

Didepside Formation by the Nonreducing Polyketide Synthase Preu6 of Preussia isomera Requires Interaction of Starter Acyl Transferase and Thioesterase Domains

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