Comparative genome mining and heterologous expression of an orphan NRPS gene cluster direct the production of ashimides

Shi, Jing; Zeng, Ying; Zhang, Bo; Shao, Fen Li; Chen, Yan Chi; Xu, Xiang; Sun, Yang; Xu, Qiang; Tan, Ren Xiang; Ge, Hui

doi:10.1039/c8sc05670f

Cited by 46 publications

(57 citation statements)

References 34 publications

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“…Terpene biosynthesis related clusters were the most abundant type of clusters observed in the CN732 genome. Out of the 22 potential biosynthetic clusters, 15 exhibited some level of similarities with known BGC whereas 7 clusters represented orphan BGCs for which no known homologous gene clusters [19] could be identified. Notably, non-ribosomal peptide synthetase and melanin type clusters shared similarity with those for antibacterial compounds, whereas the majority of polyketide, peptide or hybrid type clusters shared similarity with those for anticancer or antiparasitic compounds.…”

Section: Biosynthetic Gene Clusters For Secondary Metabolites Of Stramentioning

confidence: 99%

Genome-based analysis for the bioactive potential of Streptomyces yeochonensis CN732, an acidophilic filamentous soil actinobacterium

et al. 2020

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Background: Acidophilic members of the genus Streptomyces can be a good source for novel secondary metabolites and degradative enzymes of biopolymers. In this study, a genome-based approach on Streptomyces yeochonensis CN732, a representative neutrotolerant acidophilic streptomycete, was employed to examine the biosynthetic as well as enzymatic potential, and also presence of any genetic tools for adaptation in acidic environment. Results: A high quality draft genome (7.8 Mb) of S. yeochonensis CN732 was obtained with a G + C content of 73.53% and 6549 protein coding genes. The in silico analysis predicted presence of multiple biosynthetic gene clusters (BGCs), which showed similarity with those for antimicrobial, anticancer or antiparasitic compounds. However, the low levels of similarity with known BGCs for most cases suggested novelty of the metabolites from those predicted gene clusters. The production of various novel metabolites was also confirmed from the combined high performance liquid chromatography-mass spectrometry analysis. Through comparative genome analysis with related Streptomyces species, genes specific to strain CN732 and also those specific to neutrotolerant acidophilic species could be identified, which showed that genes for metabolism in diverse environment were enriched among acidophilic species. In addition, the presence of strain specific genes for carbohydrate active enzymes (CAZyme) along with many other singletons indicated uniqueness of the genetic makeup of strain CN732. The presence of cysteine transpeptidases (sortases) among the BGCs was also observed from this study, which implies their putative roles in the biosynthesis of secondary metabolites. Conclusions: This study highlights the bioactive potential of strain CN732, an acidophilic streptomycete with regard to secondary metabolite production and biodegradation potential using genomics based approach. The comparative genome analysis revealed genes specific to CN732 and also those among acidophilic species, which could give some insights into the adaptation of microbial life in acidic environment.

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Section: Biosynthetic Gene Clusters For Secondary Metabolites Of Stramentioning

confidence: 99%

Genome-based analysis for the bioactive potential of Streptomyces yeochonensis CN732, an acidophilic filamentous soil actinobacterium

et al. 2020

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“…Omnipeptin (Libis et al, 2019) Anisomycin (Zheng et al, 2017) Ashimides (Shi et al, 2019) Frigocyclinone (Mo et al, 2019) Locillomycins (Luo et al, 2019) PAC/BAC libraries…”

Section: Dna Fragmentationmentioning

confidence: 99%

Bioprospecting Through Cloning of Whole Natural Product Biosynthetic Gene Clusters

Lin

Nielsen

Liu

2020

Front. Bioeng. Biotechnol.

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Since the discovery of penicillin, natural products and their derivatives have been a valuable resource for drug discovery. With recent development of genome mining approaches in the post-genome era, a great number of natural product biosynthetic gene clusters (BGCs) have been identified and these can potentially be exploited for the discovery of novel natural products that can find application as pharmaceuticals. Since many BGCs are silent or do not express in native hosts under laboratory conditions, heterologous expression of BGCs in genetically tractable hosts becomes an attractive route to activate these BGCs to discover the corresponding products. Here, we highlight recent achievements in cloning and discovery of natural product biosynthetic pathways via intact BGC capturing, and discuss the prospects of high-throughput and multiplexed cloning of rational-designed gene clusters in the future.

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“…Furthermore, the performic acid generated in situ could react with the exocyclic double bond of the protoanemonin (2) via a chemoselective epoxidation reaction (Scheme 4), [5a,20] followed by a nucleophilic attack of water for the opening of an epoxide ring to afford 5-hydroxy-5-(hydroxymethyl)furan-2(5H)one (IV). [21] It is important to mention that intermediate IV is mainly found as tautomer (Z)-5-hydroxy-4-oxopent-2-enoic acid (3) due to the presence of formic acid in the reaction medium. [22] The tautomer 3 was identified in the 1 H NMR spectrum by the cis coupling constant between protons of the Scheme 3.…”

Section: Self-catalysed Oxidation Process: Generation Of Formic Acid mentioning

confidence: 99%

Obtaining Protoanemonin through Selective Oxidation of D‐Fructose and 5‐(Hydroxymethyl)furfural in a Self‐catalysed Reaction

et al. 2020

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Although different ways of converting 5-(hydroxymethyl)furfural (1) to various substrates with high value have been sought, few transformations have obtained building blocks that can be very useful in the area of fine chemistry. Herein, we report the synthesis of protoanemonin (5-methylenefuran-2(5H)-one) from D-fructose via compound (1), a versatile γ-alkylidenebutenolide, using an efficient selfcatalysed process with formic acid, with high reaction performance and selectivity (up to 94% yield and 98% conversion from (1), while 28% yield from D-fructose). This efficient and simple operational process involved a two-phase aqueous-organic system between chlorinated solvents (CH x Cl y) and hydrogen peroxide as the initial oxidizing agent. The reaction presents a key cleavage in the 5-hydroxymethyl moiety of (1), due to the Baeyer-Villiger oxidation (BVO) process that generates formic acid in situ. Ultimately, DFF and HMF were successfully obtained in 80% and 98% yield, respectively, starting from D-fructose and using Preyssler heteropolyacids as Brønsted acid catalysts under an atmosphere of oxygen in the absence of hydrogen peroxide.

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Comparative genome mining and heterologous expression of an orphan NRPS gene cluster direct the production of ashimides

Abstract: Genome mining and heterologous expression of an orphan cluster led to the discovery of ashimides featuring an unusual cyclization mechanism.

Cited by 46 publications

References 34 publications

Genome-based analysis for the bioactive potential of Streptomyces yeochonensis CN732, an acidophilic filamentous soil actinobacterium

Genome-based analysis for the bioactive potential of Streptomyces yeochonensis CN732, an acidophilic filamentous soil actinobacterium

Bioprospecting Through Cloning of Whole Natural Product Biosynthetic Gene Clusters

Obtaining Protoanemonin through Selective Oxidation of D‐Fructose and 5‐(Hydroxymethyl)furfural in a Self‐catalysed Reaction

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