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Journal ArticleDOI

Genome Mining-Driven Discovery of 5-Methylorsellinate-Derived Meroterpenoids from Aspergillus funiculosus.

16 Apr 2021-Organic Letters (American Chemical Society)-Vol. 23, Iss: 8, pp 3211-3215
TL;DR: In the fungus Aspergillus funiculosus CBS 11656 as discussed by the authors, the discovery of four new meroterpenoids (funiculolides A-D (1-4) derived from the aromatic polyketide 5-methylorsellinic acid (5-MOA) was reported.
About: This article is published in Organic Letters.The article was published on 2021-04-16. It has received 13 citations till now. The article focuses on the topics: Polyketide & Heterologous expression.
Citations
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Journal ArticleDOI
TL;DR: Characterization of an orphan biosynthetic gene cluster found in the fungus Aspergillus candidus CBS 102.13 resulted in the discovery of a pyrrolobenzazepine alkaloid, aspcandine, which is synthesized by the nonribosomal peptide synthetase-polyketide synthase hybrid AcdB, which unusually incorporates 3-hydroxy-l-kynurenine as a building block.

11 citations

Journal ArticleDOI
TL;DR: The tailoring enzymes encoded by the two clusters, collectively obtained 17 new meroterpenoids, and successfully proposed biosynthetic routes leading to apparent end products of both pathways are characterized.
Abstract: The aromatic polyketide 3,5-dimethylorsellinic acid (DMOA) serves as a precursor for many fungal meroterpenoids. A large portion of DMOA-derived meroterpenoids are biosynthesized via the cyclization of (6R,10′R)-epoxyfarnesyl-DMOA methyl ester (1). Theoretically, although 1 can be cyclized into many products, only three cyclization modes have been reported. Here, we discovered a meroterpenoid biosynthetic gene cluster in Aspergillus insuetus CBS 107.25, which encodes the biosynthetic enzymes for 1 along with a terpene cyclase that is phylogenetically distantly related to the other characterized cyclases of 1. Intriguingly, InsA7, the terpene cyclase, folds 1 in a pre-boat-chair conformation, generating a new meroterpenoid species with an axially oriented hydroxy group at C3. The A. insuetus strain also harbors an additional gene cluster encoding another cyclase of 1. The second terpene cyclase–InsB2–also synthesizes a new cyclized product of 1, thereby leading to diverging of the biosynthetic pathway in the fungus. Finally, we characterized the tailoring enzymes encoded by the two clusters, collectively obtained 17 new meroterpenoids, and successfully proposed biosynthetic routes leading to apparent end products of both pathways.

6 citations

Journal ArticleDOI
TL;DR: In this paper, a support vector machine (SVM) trained with MAP4 correctly assigned the origin for 94% of plant, 89% of fungal, and 89% bacterial NPs in this subset.
Abstract: Natural products (NPs) represent one of the most important resources for discovering new drugs. Here we asked whether NP origin can be assigned from their molecular structure in a subset of 60,171 NPs in the recently reported Collection of Open Natural Products (COCONUT) database assigned to plants, fungi, or bacteria. Visualizing this subset in an interactive tree-map (TMAP) calculated using MAP4 (MinHashed atom pair fingerprint) clustered NPs according to their assigned origin ( https://tm.gdb.tools/map4/coconut_tmap/ ), and a support vector machine (SVM) trained with MAP4 correctly assigned the origin for 94% of plant, 89% of fungal, and 89% of bacterial NPs in this subset. An online tool based on an SVM trained with the entire subset correctly assigned the origin of further NPs with similar performance ( https://np-svm-map4.gdb.tools/ ). Origin information might be useful when searching for biosynthetic genes of NPs isolated from plants but produced by endophytic microorganisms.

5 citations

Journal ArticleDOI
TL;DR: Zhang et al. as mentioned in this paper summarized the representative studies on the biosynthesis of fungal secondary metabolites by gene knockout and heterologous expression under the fungal genome mining in the last three years.
Abstract: The in-depth study of fungal secondary metabolites (SMs) over the past few years has led to the discovery of a vast number of novel fungal SMs, some of which possess good biological activity. However, because of the limitations of the traditional natural product mining methods, the discovery of new SMs has become increasingly difficult. In recent years, with the rapid development of gene sequencing technology and bioinformatics, new breakthroughs have been made in the study of fungal SMs, and more fungal biosynthetic gene clusters of SMs have been discovered, which shows that the fungi still have a considerable potential to produce SMs. How to study these gene clusters to obtain a large number of unknown SMs has been a research hotspot. With the continuous breakthrough of molecular biology technology, gene manipulation has reached a mature stage. Methods such as gene knockout and heterologous expression techniques have been widely used in the study of fungal SM biosynthesis and have achieved good effects. In this review, the representative studies on the biosynthesis of fungal SMs by gene knockout and heterologous expression under the fungal genome mining in the last three years were summarized. The techniques and methods used in these studies were also briefly discussed. In addition, the prospect of synthetic biology in the future under this research background was proposed.

3 citations

Journal ArticleDOI
TL;DR: The genome of Amphichorda felina SYSU-MS7908 was sequenced, and the identification of two new α-pyrone derivatives, amphichopyrone A and B, along with a known compound, udagawanone A (3), and anti-inflammatory activities were performed.
Abstract: Culturing ascidian-derived fungus Amphichorda felina SYSU-MS7908 under standard laboratory conditions mainly yielded meroterpenoid, and nonribosomal peptide-type natural products. We sequenced the genome of Amphichorda felina SYSU-MS7908 and found 56 biosynthetic gene clusters (BGCs) after bioinformatics analysis, suggesting that the majority of those BGCSs are silent. Here we report our genome mining effort on one cryptic BGC by heterologous expression in Aspergillus oryzae NSAR1, and the identification of two new α-pyrone derivatives, amphichopyrone A (1) and B (2), along with a known compound, udagawanone A (3). Anti-inflammatory activities were performed, and amphichopyrone A (1) and B (2) displayed potent anti-inflammatory activity by inhibiting nitric oxide (NO) production in RAW264.7 cells with IC50 values 18.09 ± 4.83 and 7.18 ± 0.93 μM, respectively.

3 citations

References
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Journal ArticleDOI
TL;DR: Easyfig is a Python application for creating linear comparison figures of multiple genomic loci with an easy-to-use graphical user interface, enabling a rapid transition between analysis and the preparation of publication quality figures.
Abstract: Easyfig is a Python application for creating linear comparison figures of multiple genomic loci with an easy-to-use graphical user interface. BLAST comparisons between multiple genomic regions, ranging from single genes to whole prokaryote chromosomes, can be generated, visualized and interactively coloured, enabling a rapid transition between analysis and the preparation of publication quality figures. © The Author(s) 2011. Published by Oxford University Press.

2,344 citations

Journal ArticleDOI
TL;DR: This review deals with the isolation and structure elucidation of meroterpenoids from higher and lower fungi, and discusses biosynthetic studies and biological activities as appropriate.

316 citations

Journal ArticleDOI
TL;DR: This review summarizes the molecular bases for their biosyntheses, which were recently elucidated with modern techniques, and also discusses the plausible biosynthetic pathways of other related natural products lacking genetic information.

260 citations

Journal ArticleDOI
TL;DR: The aim of this review is to draw up a comprehensive inventory of the less commonly encountered 1,n-radical translocations (n≠5) with the aim to update this topic with the most recent relevant data.
Abstract: Hydrogen-atom transfer (HAT) counts amongst the most widely investigated routes to carbon-centered radicals. Intramolecular processes involving 1,5-HAT are widespread to promote regioselective radical "CH activation". The aim of this review is to draw up a comprehensive inventory of the less commonly encountered 1,n-radical translocations (n≠5) with the aim to update this topic with the most recent relevant data.

172 citations

Journal ArticleDOI
TL;DR: Results obtained showed that the adeA gene served as an efficient selection marker in developing a novel host-vector system with quadruple auxotrophy in A. oryzae, thus providing a powerful tool to breed multiple auxotrophic mutants from a deuteromycete wherein sexual crossing is impossible.
Abstract: We previously designed a triple auxotrophic host-vector system in Aspergillus oryzae by isolating red-colored adenine auxotrophic mutants upon UV mutagenesis of a double auxotrophic host (niaD−sC−). In the present study an effort to exploit this system and construct a novel quadruple auxotrophic host was made by disrupting the argB gene involved in arginine biosynthesis. The argB gene-disruption cassette was generated by fusion PCR, which required only two steps of PCR to insert the selectable marker, adeA, into the target argB gene. The chimeric DNA fragment was transformed into the triple auxotrophic strain (niaD−sC−adeA−) and the argB disruptants were obtained with a high rate of efficiency (approximately 40%). The argB disruptants were characterized by normal colony color and reversal of arginine auxotrophy by introduction of the wild-type argB gene. Quadruple auxotrophic strains (niaD−sC−ΔargB adeA− or niaD−sC−ΔargB adeB−) were subsequently isolated upon UV mutagenesis of the triple auxotrophic strain (niaD−sC−ΔargB) followed by screening of red-colored colonies for adenine auxotrophy. The results obtained showed that the adeA gene served as an efficient selection marker in developing a novel host-vector system with quadruple auxotrophy in A. oryzae, thus providing a powerful tool to breed multiple auxotrophic mutants from a deuteromycete wherein sexual crossing is impossible.

159 citations

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