Dalmanol biosyntheses require coupling of two separate polyketide gene clusters

Zhou, Zhen; Zhu, Hong; Lin, Liang‐Hung; Zhang, Xuan; Ge, Hui; Jiao, Rui Hua; Tan, Ren Xiang

doi:10.1039/c8sc03697g

Cited by 22 publications

(39 citation statements)

References 63 publications

(111 reference statements)

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“…In almost all known cases the catalytic domains are cis-acting: that is, they are part of the covalent complex. However, in some cases trans-acting enoyl reductase (ER) [4] and (very rarely) trans-C-methyl transferase (C-MeT) [5] and trans-KR domains [6] are known. Other trans-acting interactions are also possible.…”

Section: Introductionmentioning

confidence: 99%

“…[1,2] Fungal highly reducing (hr) PKS resemble mammalian fatty acid synthases [3] (mFAS) in domain organisation, while fungal non-reducing (nr) PKS are simpler and lack ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) b-processing domains.I na lmost all known cases the catalytic domains are cis-acting:that is,they are part of the covalent complex. However,insome cases trans-acting enoyl reductase (ER) [4] and (very rarely) trans-C-methyl transferase (C-MeT) [5] and trans-KR domains [6] are known. Other trans-acting interactions are also possible.F or example nr-PKS usually have as tarter-unit acyl transferase (SAT) domain which can accept an acyl chain priming unit directly from the acyl carrier protein (ACP) of an hr-PKS or FAS.…”

Section: Introductionmentioning

confidence: 99%

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Biosynthesis of 6‐Hydroxymellein Requires a Collaborating Polyketide Synthase‐like Enzyme

et al. 2021

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The polyketide synthase (PKS)-like protein TerB, consisting of inactive dehydratase, inactive C-methyltransferase, and functional ketoreductase domains collaborates with the iterative non reducing PKS TerA to produce 6-hydroxymellein, a key pathway intermediate during the biosynthesis of various fungal natural products. The catalytically inactive dehydratase domain of TerB appears to mediate productive interactions with TerA, demonstrating a new mode of transinteraction between iterative PKS components.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biosynthesis of 6‐Hydroxymellein Requires a Collaborating Polyketide Synthase‐like Enzyme

et al. 2021

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“…4 A) most of the GCFs (172) could not be correlated to a specific product or product family. Among those PKS GCFs where product prediction is feasible is a large network composed of nrPKS BGCs known to be responsible for naphthalene formation ( Fulton et al ., 1999 , Zhou et al 2019 ) and their homologs from the Hypoxylaceae and X. hypoxylon genomes (see DHN section for detailed discussion). Another PKS GCF contained multiple literature-described prPKS involved in the biosynthesis of 6-methylsalicylic acid or mellein, and compounds derived thereof ( Fujii et al ., 1996 , Lu et al ., 2005 , Chooi et al 2015 ).…”

Section: Resultsmentioning

confidence: 99%

Secondary metabolite biosynthetic diversity in the fungal family Hypoxylaceae and Xylaria hypoxylon

Kuhnert

Navarro-Muñoz

Becker

et al. 2021

Studies in Mycology

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To date little is known about the genetic background that drives the production and diversification of secondary metabolites in the Hypoxylaceae . With the recent availability of high-quality genome sequences for 13 representative species and one relative ( Xylaria hypoxylon ) we attempted to survey the diversity of biosynthetic pathways in these organisms to investigate their true potential as secondary metabolite producers. Manual search strategies based on the accumulated knowledge on biosynthesis in fungi enabled us to identify 783 biosynthetic pathways across 14 studied species, the majority of which were arranged in biosynthetic gene clusters (BGC). The similarity of BGCs was analysed with the BiG-SCAPE engine which organised the BGCs into 375 gene cluster families (GCF). Only ten GCFs were conserved across all of these fungi indicating that speciation is accompanied by changes in secondary metabolism. From the known compounds produced by the family members some can be directly correlated with identified BGCs which is highlighted herein by the azaphilone, dihydroxynaphthalene, tropolone, cytochalasan, terrequinone, terphenyl and brasilane pathways giving insights into the evolution and diversification of those compound classes. Vice versa , products of various BGCs can be predicted through homology analysis with known pathways from other fungi as shown for the identified ergot alkaloid, trigazaphilone, curvupallide, viridicatumtoxin and swainsonine BGCs. However, the majority of BGCs had no obvious links to known products from the Hypoxylaceae or other well-studied biosynthetic pathways from fungi. These findings highlight that the number of known compounds strongly underrepresents the biosynthetic potential in these fungi and that a tremendous number of unidentified secondary metabolites is still hidden. Moreover, with increasing numbers of genomes for further Hypoxylaceae species becoming available, the likelihood of revealing new biosynthetic pathways that encode new, potentially useful compounds will significantly improve. Reaching a better understanding of the biology of these producers, and further development of genetic methods for their manipulation, will be crucial to access their treasures.

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“…Owing to its production of a series of bioactive naphthol radical polymerized metabolites with undescribed architectures, the mantis-associated fungus Daldinia eschscholzii IFB-TL01 has attracted remarkable attention 8–13 . As part of our continuing research on discovery of anti-fibrotic metabolites, the EtOAc extract of the D. eschscholzii culture was selected for investigation.…”

Section: Resultsmentioning

confidence: 99%

Galewone, an Anti-Fibrotic Polyketide from Daldinia eschscholzii with an Undescribed Carbon Skeleton

Zhang

Jiang

Wang

et al. 2019

Sci Rep

Self Cite

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A novel polyphenolic natural product, galewone, with undescribed carbon skeleton, was isolated as a racemate from the culture of Daldinia eschscholzii IFB-TL01, a fungus obtained from the mantis (Tenodera aridifolia) gut. The galewone structure was elucidated by a combination of MS and NMR spectra, and substantiated by X-ray crystallographic diffraction. The absolute stereochemistry of each galewone enantiomers was determined by the CD spectrum. In compliance of the structural similarities, galewone might be the shunt products of the dalesconol biosynthetic pathway. Both (−)- and ( + )-galewones were evaluated to be anti-fibrotic against activated hepatic stellate cell line, CFSC-8B, with the IC50 values being 3.73 ± 0.21 and 10.10 ± 0.41 μM, respectively. Thus, galewone may serve as a starting molecule for the discovery of new anti-fibrotic drug.

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Dalmanol biosyntheses require coupling of two separate polyketide gene clusters

Abstract: Polyketide–polyketide hybrids are unique natural products with promising bioactivity, but the hybridization processes remain poorly understood.

Cited by 22 publications

References 63 publications

Biosynthesis of 6‐Hydroxymellein Requires a Collaborating Polyketide Synthase‐like Enzyme

Biosynthesis of 6‐Hydroxymellein Requires a Collaborating Polyketide Synthase‐like Enzyme

Secondary metabolite biosynthetic diversity in the fungal family Hypoxylaceae and Xylaria hypoxylon

Galewone, an Anti-Fibrotic Polyketide from Daldinia eschscholzii with an Undescribed Carbon Skeleton

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