Abyssomicins—A 20-Year Retrospective View

Fiedler, Hans‐Peter

doi:10.3390/md19060299

Cited by 11 publications

(13 citation statements)

References 25 publications

(39 reference statements)

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“…In addition, the aziridine alkaloid antibiotic ficellomycin (3% gene identity) and the type I PKs compounds tetarimycin A and B (3% gene identity) inhibit multi-drug resistant S. aureus strains (Kallifidas et al 2012 ; He et al 2018 ). The N. aurea strain also has the capacity to produce abyssomicin C/ atrop -abyssomicin C (25% gene similarity), polycyclic macrolactones, first detected in the type strain of Verrucosispora maris (now Micromonospora maris ) (Nouioui et al 2018 ), which show pronounced activity against multi-drug resistant Gram-positive bacteria (Fiedler 2021 ). Additional compounds associated with each of the strains are shown in Table 3 .…”

Section: Resultsmentioning

confidence: 99%

Nocardia noduli sp. nov., a novel actinobacterium with biotechnological potential

et al. 2022

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A genome-based polyphasic study was undertaken to establish the taxonomic status of an actinobacterium strain isolated from an actinorhizal root nodule. Strain ncl1T was found to have chemotaxonomic, cultural and morphological properties characteristic of members of the genus Nocardia. The strain was closely related to Nocardia aurea in the phylogenetic trees based on 16S rRNA gene and genome sequences. The draft genome of the strain is 8.9 Mbp in size, has a genomic DNA G + C content of 67.0% and was predicted to contain at least 19 biosynthetic gene clusters encoding for specialized metabolites. Strain ncl1T was distinguished from its closest neighbour, N. aurea DSM 103986T, by a broad range of phenotypic properties and by low average nucleotide identity and digital DNA-DNA hybridization scores. Consequently, the strain represents a novel Nocardia species for which the name Nocardia noduli sp. nov. is proposed. The type strain is ncl1T (CECT 30123T = DSM 110878T). The present study provides further evidence that actinorhizal nodules are a source of novel species of Nocardia.

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Section: Resultsmentioning

confidence: 99%

Nocardia noduli sp. nov., a novel actinobacterium with biotechnological potential

et al. 2022

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“…The gene locus ctg1_2037 was predicted to be a FAD-dependent bifunctional oxygenase/reductase with an N-terminal flavin-dependent oxygenase domain and a C-terminal reductase domain, which belongs to the short-chain dehydrogenase/reductase (SDR) superfamily [33]. The gene locus (ctg1_2037) was predicted to be involved in the transformation from 8 to intermediate 7 and then to aglycone tetrangomycin (6). At this stage, tetrangomycin was proposed to be transformed into 2-hydro-tetrangomycin (2) through the hydrogenation reaction that occurred at the C-2 position catalyzed by the hydrolase (ctg1_2029), which was regarded as the main intermediate reaction in the angucycline/angucyclinone derivative biosynthetic pathway in strain NJES-13 T .…”

Section: Proposed Biogenetic Pathway For Three Ad Metabolitesmentioning

confidence: 99%

“…The angucycline/angucyclinone (sugarless) derivatives (ADs), which are aromatic polyketides with a tetracyclic benz[a]anthracene skeleton, include the largest group of polyketide synthase (PKS)-engineered natural products and comprise a rapidly growing class of bioactive secondary metabolites derived from a variety of microbial sources [5][6][7]. Among plenty of ADs, gephyromycin, which was originally isolated from Streptomyces griseus in 2005, is the first representative angucyclinone with an unprecedented intramolecular ether bridge [8].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.

et al. 2021

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Strain NJES-13T is the type strain and currently the only species of the newly established actinobacteria genera Aptenodytes in the family Dermatophilaceae isolated from the gut microbiota of the Antarctic emperor penguin. This strain demonstrated excellent bioflocculation activity with bacteria-derived exopolysaccharides (EPSs). Moreover, it produced bioactive angucycline/angucyclinone derivatives (ADs) and contained one type III polyketide synthase (T3PKS), thus demonstrating great potential to produce novel bioactive compounds. However, the low productivity of the potential new AD metabolite was the main obstacle for its chemical structure elucidation. In this study, to increase the concentration of targeted metabolites, the influence of cellular morphology on AD metabolism in strain NJES-13T was determined using glass bead-enhanced fermentation. Based on the cellular ultra-structural observation driven by bacterial EPSs, and quantitative analysis of the targeted metabolites, the successful increasing of the productivity of three AD metabolites was achieved. Afterward, a new frigocyclinone analogue was isolated and then identified as 2-hydroxy-frigocyclinone, as well as two other known ADs named 2-hydroxy-tetrangomycin (2-HT) and gephyromycin (GPM). Three AD metabolites were found to demonstrate different bioactivities. Both C-2 hydroxyl substitutes, 2-hydroxy-tetrangomycin and 2-hydroxy-frigocyclinone, exhibited variable inhibitory activities against Staphylococcus aureus, Bacillus subtilis and Candida albicans. Moreover, the newly identified 2-hydroxy-frigocyclinone also showed significant cytotoxicity against three tested human-derived cancerous cell lines (HL-60, Bel-7402 and A549), with all obtained IC50 values less than 10 µM. Based on the genetic analysis after genomic mining, the plausible biogenetic pathway of the three bioactive ADs in strain NJES-13T was also proposed.

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“…40 Abyssomicins selectively inhibit the enzyme 4-amino-4-deoxychorismate synthase which catalyzes the transformation of chorismate to PABA, an intermediate in the folic acid pathway. 41…”

Section: Introductionmentioning

confidence: 99%

Antivitamins: A Silver Lining in the Era of Antimicrobial Resistance

Mahwish

Bairy

Srinivasamurthy

2022

Journal of Pharmacology and Pharmacotherapeutics

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Antivitamins are compounds that negate the biological effects of vitamins. They have been successfully exploited for the development of various classes of drugs. In the early 19th century, the antifolate prontosil was developed for the treatment of puerperal fever. Since then, numerous other antifolates have been used to treat a wide range of infections. Antifolates, such as methotrexate, are potent anticancer agents and antivitamin K, such as warfarin, are used as anticoagulants. Despite several years of research, most antivitamin-based drugs are limited to vitamin K and B9, and the development of antagonists for other vitamins is still in the nascent stage. In the era of antimicrobial resistance, antivitamins can be considered as a promising alternative to develop newer antimicrobials and are worth exploring further. This review discusses key antivitamins at different stages of development which have potential utility as antibiotic drug candidates. The summary of studies of antivitamins in clinical development is also narrated.

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Abyssomicins—A 20-Year Retrospective View

Cited by 11 publications

References 25 publications

Nocardia noduli sp. nov., a novel actinobacterium with biotechnological potential

Nocardia noduli sp. nov., a novel actinobacterium with biotechnological potential

Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.

Antivitamins: A Silver Lining in the Era of Antimicrobial Resistance

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