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10 pages, 1111 KiB

Open AccessArticle

Genomics-Driven Discovery of Benzoxazole Alkaloids from the Marine-Derived Micromonospora sp. SCSIO 07395

by Ziqian Cheng, Qingbo Zhang, Jing Peng, Xiaoyang Zhao, Liang Ma, Changsheng Zhang and Yiguang Zhu

Molecules 2023, 28(2), 821; https://doi.org/10.3390/molecules28020821 - 13 Jan 2023

Cited by 5 | Viewed by 2413

Abstract

Benzoxazole alkaloids exhibit a diverse array of structures and interesting biological activities. Herein we report the identification of a benzoxazole alkaloid-encoding biosynthetic gene cluster (mich BGC) in the marine-derived actinomycete Micromonospora sp. SCSIO 07395 and the heterologous expression of this BGC in [...] Read more.

Benzoxazole alkaloids exhibit a diverse array of structures and interesting biological activities. Herein we report the identification of a benzoxazole alkaloid-encoding biosynthetic gene cluster (mich BGC) in the marine-derived actinomycete Micromonospora sp. SCSIO 07395 and the heterologous expression of this BGC in Streptomyces albus. This approach led to the discovery of five new benzoxazole alkaloids microechmycin A–E (1–5), and a previously synthesized compound 6. Their structures were elucidated by HRESIMS and 1D and 2D NMR data. Microechmycin A (1) showed moderate antibacterial activity against Micrococcus luteus SCSIO ML01 with the minimal inhibitory concentration (MIC) value of 8 μg mL⁻¹. Full article

(This article belongs to the Special Issue Microbial Natural Products in Drug Discovery Chemistry)

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17 pages, 2068 KiB

Open AccessArticle

Production and Characterization of a Novel Exopolysaccharide from Ramlibacter tataouinensis

by Desislava Jivkova, Ganesan Sathiyanarayanan, Mourad Harir, Norbert Hertkorn, Philippe Schmitt-Kopplin, Ghislain Sanhaji, Sylvain Fochesato, Catherine Berthomieu, Alain Heyraud, Wafa Achouak, Catherine Santaella and Thierry Heulin

Molecules 2022, 27(21), 7172; https://doi.org/10.3390/molecules27217172 - 24 Oct 2022

Cited by 14 | Viewed by 2816

Abstract

The current study examines the desiccation-resistant Ramlibacter tataouinensis TTB310^T as a model organism for the production of novel exopolysaccharides and their structural features. This bacterium is able to produce dividing forms of cysts which synthesize cell-bound exopolysaccharide. Initial experiments were conducted on [...] Read more.

The current study examines the desiccation-resistant Ramlibacter tataouinensis TTB310^T as a model organism for the production of novel exopolysaccharides and their structural features. This bacterium is able to produce dividing forms of cysts which synthesize cell-bound exopolysaccharide. Initial experiments were conducted on the enrichment of cyst biomass for exopolysaccharide production under batch-fed conditions in a pilot-scale bioreactor, with lactate as the source of carbon and energy. The optimized medium produced significant quantities of exopolysaccharide in a single growth phase, since the production of exopolysaccharide took place during the division of the cysts. The exopolysaccharide layer was extracted from the cysts using a modified trichloroacetic acid method. The biochemical characterization of purified exopolysaccharide was performed by gas chromatography, ultrahigh-resolution mass spectrometry, nuclear magnetic resonance, and Fourier-transform infrared spectrometry. The repeating unit of exopolysaccharide was a decasaccharide consisting of ribose, glucose, rhamnose, galactose, mannose, and glucuronic acid with the ratio 3:2:2:1:1:1, and additional substituents such as acetyl, succinyl, and methyl moieties were also observed as a part of the exopolysaccharide structure. This study contributes to a fundamental understanding of the novel structural features of exopolysaccharide from a dividing form of cysts, and, further, results can be used to study its rheological properties for various industrial applications. Full article

(This article belongs to the Special Issue Microbial Natural Products in Drug Discovery Chemistry)

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18 pages, 1090 KiB

Open AccessArticle

Kribbellichelins A and B, Two New Antibiotics from Kribbella sp. CA-293567 with Activity against Several Human Pathogens

by Jorge R. Virués-Segovia, Fernando Reyes, Sandra Ruíz, Jesús Martín, Ignacio Fernández-Pastor, Carlos Justicia, Mercedes de la Cruz, Caridad Díaz, Thomas A. Mackenzie, Olga Genilloud, Ignacio González and José R. Tormo

Molecules 2022, 27(19), 6355; https://doi.org/10.3390/molecules27196355 - 26 Sep 2022

Cited by 5 | Viewed by 3845

Abstract

Current needs in finding new antibiotics against emerging multidrug-resistant superbugs are pushing the scientific community into coming back to Nature for the discovery of novel active structures. Recently, a survey of halophilic actinomyectes from saline substrates of El Saladar del Margen, in [...] Read more.

Current needs in finding new antibiotics against emerging multidrug-resistant superbugs are pushing the scientific community into coming back to Nature for the discovery of novel active structures. Recently, a survey of halophilic actinomyectes from saline substrates of El Saladar del Margen, in the Cúllar-Baza depression (Granada, Spain), led us to the isolation and identification of 108 strains from the rhizosphere of the endemic plant Limonium majus. Evaluation of the potential of these strains to produce new anti-infective agents against superbug pathogens was performed through fermentation in 10 different culture media using an OSMAC approach and assessment of the antibacterial and antifungal properties of their acetone extracts. The study allowed the isolation of two novel antibiotic compounds, kribbellichelin A (1) and B (2), along with the known metabolites sandramycin (3), coproporphyrin III (4), and kribelloside C (5) from a bioassay-guided fractionation of scaled-up active extracts of the Kribbella sp. CA-293567 strain. The structures of the new molecules were elucidated by ESI-qTOF-MS/MS, 1D and 2D NMR, and Marfey’s analysis for the determination of the absolute configuration of their amino acid residues. Compounds 1–3 and 5 were assayed against a panel of relevant antibiotic-resistant pathogenic strains and evaluated for cytotoxicity versus the human hepatoma cell line HepG2 (ATCC HB-8065). Kribbellichelins A (1) and B (2) showed antimicrobial activity versus Candida albicans ATCC-64124, weak potency against Acinetobacter baumannii MB-5973 and Pseudomonas aeruginosa MB-5919, and an atypical dose-dependent concentration profile against Aspergillus fumigatus ATCC-46645. Sandramycin (3) confirmed previously reported excellent growth inhibition activity against MRSA MB-5393 but also presented clear antifungal activity against C. albicans ATCC-64124 and A. fumigatus ATCC-46645 associated with lower cytotoxicity observed in HepG2, whereas Kribelloside C (5) displayed high antifungal activity only against A. fumigatus ATCC-46645. Herein, we describe the processes followed for the isolation, structure elucidation, and potency evaluation of these two new active compounds against a panel of human pathogens as well as, for the first time, the characterization of the antifungal activities of sandramycin (3). Full article

(This article belongs to the Special Issue Microbial Natural Products in Drug Discovery Chemistry)

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9 pages, 895 KiB

Open AccessArticle

Two New Triterpenes from Basidiomata of the Medicinal and Edible Mushroom, Laetiporus sulphureus

by Khadija Hassan, Blondelle Matio Kemkuignou and Marc Stadler

Molecules 2021, 26(23), 7090; https://doi.org/10.3390/molecules26237090 - 24 Nov 2021

Cited by 18 | Viewed by 3231

Abstract

In the search for novel anti-infectives from natural sources, fungi, in particular basidiomycetes, have proven to still harbor so much potential in terms of secondary metabolites diversity. There have been numerous reports on isolating numerous secondary metabolites from genus Laetiporus. This study [...] Read more.

In the search for novel anti-infectives from natural sources, fungi, in particular basidiomycetes, have proven to still harbor so much potential in terms of secondary metabolites diversity. There have been numerous reports on isolating numerous secondary metabolites from genus Laetiporus. This study reports on two new triterpenoids, laetiporins C and D, and four known triterpenes from the fruiting body of L. sulphureus. The structures of the isolated compounds were elucidated based on their 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data in combination with high-resolution electrospray mass spectrometric (HR-ESIMS) data. Laetiporin C exhibited weak antifungal activity against Mucor hiemalis. Furthermore, the compounds showed weak antiproliferative activity against the mouse fibroblast L929 and human cancer cell lines, including KB-3-1, A431, MCF-7, PC-3 and A549. Full article

(This article belongs to the Special Issue Microbial Natural Products in Drug Discovery Chemistry)

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10 pages, 3549 KiB

Open AccessArticle

New Scabimycins A-C Isolated from Streptomyces acidiscabies (Lu19992)

by Constanze Paulus, Josef Zapp and Andriy Luzhetskyy

Molecules 2021, 26(19), 5922; https://doi.org/10.3390/molecules26195922 - 29 Sep 2021

Cited by 1 | Viewed by 2270

Abstract

Peptide natural products displaying a wide range of biological activities have become important drug candidates over the years. Microorganisms have been a powerful source of such bioactive peptides, and Streptomyces have yielded many novel natural products thus far. In an effort to uncover [...] Read more.

Peptide natural products displaying a wide range of biological activities have become important drug candidates over the years. Microorganisms have been a powerful source of such bioactive peptides, and Streptomyces have yielded many novel natural products thus far. In an effort to uncover such new, meaningful compounds, the metabolome of Streptomyces acidiscabies was analyzed thoroughly. Three new compounds, scabimycins A–C (1–3), were discovered, and their chemical structures were elucidated by NMR spectroscopy. The relative and absolute configurations were determined using ROESY NMR experiments and advanced Marfey’s method. Full article

(This article belongs to the Special Issue Microbial Natural Products in Drug Discovery Chemistry)

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11 pages, 1720 KiB

Open AccessArticle

PTP1B Inhibitory Secondary Metabolites from an Antarctic Fungal Strain Acremonium sp. SF-7394

by Hye Jin Kim, Xiao-Jun Li, Dong-Cheol Kim, Tai Kyoung Kim, Jae Hak Sohn, Haeun Kwon, Dongho Lee, Youn-Chul Kim, Joung Han Yim and Hyuncheol Oh

Molecules 2021, 26(18), 5505; https://doi.org/10.3390/molecules26185505 - 10 Sep 2021

Cited by 8 | Viewed by 2688

Abstract

Chemical investigation of the Antarctic lichen-derived fungal strain Acremonium sp. SF-7394 yielded a new amphilectane-type diterpene, acrepseudoterin (1), and a new acorane-type sesquiterpene glycoside, isocordycepoloside A (2). In addition, three known fungal metabolites, (−)-ternatin (3), [D-Leu]-ternatin ( [...] Read more.

Chemical investigation of the Antarctic lichen-derived fungal strain Acremonium sp. SF-7394 yielded a new amphilectane-type diterpene, acrepseudoterin (1), and a new acorane-type sesquiterpene glycoside, isocordycepoloside A (2). In addition, three known fungal metabolites, (−)-ternatin (3), [D-Leu]-ternatin (4), and pseurotin A (5), were isolated from the EtOAc extract of the fungal strain. Their structures were mainly elucidated by analyzing their NMR and MS data. The absolute configuration of 1 was proposed by electronic circular dichroism calculations, and the absolute configuration of the sugar unit in 2 was determined by a chemical method. The inhibitory effects of the isolated compounds on protein tyrosine phosphatase 1B (PTP1B) were evaluated by enzymatic assays; results indicated that acrepseudoterin (1) and [D-Leu]-ternatin (4) dose-dependently inhibited the enzyme activity with IC₅₀ values of 22.8 ± 1.1 μM and 14.8 ± 0.3 μM, respectively. Moreover, compound 1 was identified as a competitive inhibitor of PTP1B. Full article

(This article belongs to the Special Issue Microbial Natural Products in Drug Discovery Chemistry)

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7 pages, 589 KiB

Open AccessArticle

Nitrogenous Compounds from the Antarctic Fungus Pseudogymnoascus sp. HSX2#-11

by Ting Shi, Li Zheng, Xiang-Qian Li, Jia-Jia Dai, Yi-Ting Zhang, Yan-Yan Yu, Wen-Peng Hu and Da-Yong Shi

Molecules 2021, 26(9), 2636; https://doi.org/10.3390/molecules26092636 - 30 Apr 2021

Cited by 2 | Viewed by 2466

Abstract

The species Pseudogymnoascus is known as a psychrophilic pathogenic fungus which is ubiquitously distributed in Antarctica. While the studies of its secondary metabolites are infrequent. Systematic research of the metabolites of the Antarctic fungus Pseudogymnoascus sp. HSX2#-11 led to the isolation of one [...] Read more.

The species Pseudogymnoascus is known as a psychrophilic pathogenic fungus which is ubiquitously distributed in Antarctica. While the studies of its secondary metabolites are infrequent. Systematic research of the metabolites of the Antarctic fungus Pseudogymnoascus sp. HSX2#-11 led to the isolation of one new pyridine derivative, 4-(2-methoxycarbonyl-ethyl)-pyridine-2-carboxylic acid methyl ester (1), together with one pyrimidine, thymine (2), and eight diketopiperazines, cyclo-(dehydroAla-l-Val) (3), cyclo-(dehydroAla-l-Ile) (4), cyclo-(dehydroAla-l-Leu) (5), cyclo-(dehydroAla-l-Phe) (6), cyclo-(l-Val-l-Phe) (7), cyclo-(l-Leu-l-Phe) (8), cyclo-(l-Trp-l-Ile) (9) and cyclo-(l-Trp-l-Phe) (10). The structures of these compounds were established by extensive spectroscopic investigation, as well as by detailed comparison with literature data. This is the first report to discover pyridine, pyrimidine and diketopiperazines from the genus of Pseudogymnoascus. Full article

(This article belongs to the Special Issue Microbial Natural Products in Drug Discovery Chemistry)

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Review

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29 pages, 3208 KiB

Open AccessReview

Classification and Multifaceted Potential of Secondary Metabolites Produced by Bacillus subtilis Group: A Comprehensive Review

by Sajid Iqbal, Farida Begum, Ali A. Rabaan, Mohammed Aljeldah, Basim R. Al Shammari, Abdulsalam Alawfi, Amer Alshengeti, Tarek Sulaiman and Alam Khan

Molecules 2023, 28(3), 927; https://doi.org/10.3390/molecules28030927 - 17 Jan 2023

Cited by 56 | Viewed by 6917

Abstract

Despite their remarkable biosynthetic potential, Bacillus subtilis have been widely overlooked. However, their capability to withstand harsh conditions (extreme temperature, Ultraviolet (UV) and γ-radiation, and dehydration) and the promiscuous metabolites they synthesize have created increased commercial interest in them as a therapeutic agent, [...] Read more.

Despite their remarkable biosynthetic potential, Bacillus subtilis have been widely overlooked. However, their capability to withstand harsh conditions (extreme temperature, Ultraviolet (UV) and γ-radiation, and dehydration) and the promiscuous metabolites they synthesize have created increased commercial interest in them as a therapeutic agent, a food preservative, and a plant-pathogen control agent. Nevertheless, the commercial-scale availability of these metabolites is constrained due to challenges in their accessibility via synthesis and low fermentation yields. In the context of this rising in interest, we comprehensively visualized the antimicrobial peptides produced by B. subtilis and highlighted their prospective applications in various industries. Moreover, we proposed and classified these metabolites produced by the B. subtilis group based on their biosynthetic pathways and chemical structures. The biosynthetic pathway, bioactivity, and chemical structure are discussed in detail for each class. We believe that this review will spark a renewed interest in the often disregarded B. subtilis and its remarkable biosynthetic capabilities. Full article

(This article belongs to the Special Issue Microbial Natural Products in Drug Discovery Chemistry)

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