Background: Diabetic foot ulcers are a frequent and serious complication of diabetes with a high risk of amputation. Exercise has been shown to promote wound healing; however, patients with non-healing foot ulcers have limited ability to exercise due to the foot ulcer. Other strategies are therefore warranted.
View Article and Find Full Text PDFFungal infections pose a great threat to public health and there are only four main types of antifungal drugs, which are often limited with toxicity, drug-drug interactions and antibiotic resistance. Streptomyces is an important source of antibiotics, represented by the clinical drug amphotericin B. Here we report the discovery of alligamycin A (1) as an antifungal compound from the rapamycin-producer Streptomyces iranensis through genome-mining, genetics and natural product chemistry approaches.
View Article and Find Full Text PDFCombinatorial library-based metabolic engineering approaches allow lower cost and faster strain development. We developed a genetic toolbox EXPRESS for combinatorial engineering of the oleaginous yeast Yarrowia lipolytica. The toolbox enables consecutive rounds of engineering, where up to three combinatorially assembled gene expression cassettes can be integrated into each yeast clone per round.
View Article and Find Full Text PDFFilamentous Actinobacteria, recently renamed Actinomycetia, are the most prolific source of microbial bioactive natural products. Studies on biosynthetic gene clusters benefit from or require chromosome-level assemblies. Here, we provide DNA sequences from >1000 isolates: 881 complete genomes and 153 near-complete genomes, representing 28 genera and 389 species, including 244 likely novel species.
View Article and Find Full Text PDFAzoxy compounds are a distinctive group of bioactive secondary metabolites characterized by a unique RN═N(O)R moiety. The azoxy moiety is present in various classes of metabolites that exhibit various biological activities. The enzymatic mechanisms underlying azoxy bond formation remain enigmatic.
View Article and Find Full Text PDFThe copepod species Acartia tonsa (Dana)(Crustacea) have the unique ability to induce quiescent embryonic dormancy if adverse environmental conditions occur; a characteristic shared by 41 other species belonging to the superfamily Centropagoida in the Calanoida order. However, the transcriptional changes characterizing this process are not known. Here, we compare the transcriptome of embryos in arrested quiescence with the normal development to identify pathways and differentially regulated transcripts involved in quiescent embryogenesis.
View Article and Find Full Text PDFMicrobiol Resour Announc
September 2023
Here, we report the complete, circular genome sequence of a potential novel species from the underexplored Alphaproteobacterial genus sp. NBC_00550 was isolated from a soil sample collected in Lyngby, Denmark. We explore the biosynthetic potential of sp.
View Article and Find Full Text PDFHere, we report the complete genome sequences of Methylorubrum extorquens NBC_00036 and NBC_00404. The genomes were sequenced using the Oxford Nanopore Technologies MinION and Illumina NovaSeq systems. Both genomes are circular, with sizes of 5,661,342 bp and 5,869,086 bp, respectively.
View Article and Find Full Text PDFJ1074 is a popular platform to discover novel natural products via the expression of heterologous biosynthetic gene clusters (BGCs). There is keen interest in improving the ability of this platform to overexpress BGCs and, consequently, enable the purification of specialized metabolites. Mutations within gene for the β-subunit of RNA polymerase are known to increase rifampicin resistance and augment the metabolic capabilities of streptomycetes.
View Article and Find Full Text PDFCrosiellidines are intriguing pyrazine-alkylguanidine metabolites isolated from the minor actinomycete genus . Their structures present an unprecedented 2-methoxy-3,5,6-trialkyl pyrazine scaffold and uncommon guanidine prenylations, including an exotic -prenylated -hydroxyguanidine moiety. The novel substitution pattern of the 2-methoxypyrazine core inaugurates a new class of naturally occurring pyrazine compounds, the biosynthetic implications of which are discussed herein.
View Article and Find Full Text PDFGlobomycin is a cyclic lipodepsipeptide originally isolated from several species which displays strong and selective antibacterial activity against Gram-negative pathogens. Its mode of action is based on the competitive inhibition of the lipoprotein signal peptidase II (LspA), which is absent in eukaryotes and considered an attractive target for the development of new antibiotics. Despite its interesting biological properties, the gene cluster encoding its biosynthesis has not yet been identified.
View Article and Find Full Text PDFComp Biochem Physiol Part D Genomics Proteomics
March 2023
The calanoid copepod Acartia tonsa (Dana) has attracted interest because of its use as a copepod model organism as well as its potential economic role as live fish larval feed. While the adult genome and transcriptome of A. tonsa has been investigated, no studies have been performed investigating the genome-wide transcriptional changes during the normal subitaneous embryogenesis.
View Article and Find Full Text PDFActinomycetota (Actinobacteria) is an ecologically and industrially important phylum which is challenging to extract pure high-molecular-weight (HMW) DNA from. This protocol provides a parallelized, cost-effective, and straightforward approach for consistently extracting pure HMW DNA using modified non-toxic commercial kits suitable for higher throughput applications. We further provide a workflow for sequencing and assembly of complete genomes using an optimized Oxford Nanopore rapid barcoding protocol and Illumina data error correction.
View Article and Find Full Text PDFIn 2020, the novel coronavirus, SARS-CoV-2, caused a pandemic, which is still raging at the time of writing this. Here, we present results from SpikeSeq, the first published Sanger sequencing-based method for the detection of Variants of Concern (VOC) and key mutations, using a 1 kb amplicon from the recognized ARTIC Network primers. The proposed setup relies entirely on materials and methods already in use in diagnostic RT-qPCR labs and on existing commercial infrastructure offering sequencing services.
View Article and Find Full Text PDFIntroduction: Diabetic foot ulcers (DFUs) are associated with extensive consequences for the affected patients and treatment of these hard-to-heal ulcers is known for being challenging. New treatment methods to supplement the current standard care may improve the prognosis for these patients.A preceding feasibility trial with promising results, facilitated this trial that aims to study the effect of a novel simple treatment, called inforatio technique, which may promote healing of DFUs.
View Article and Find Full Text PDFActinomycetes make a wealth of complex, structurally diverse natural products, and a key challenge is to link them to their biosynthetic gene clusters and delineate the reactions catalyzed by each of the enzymes. Here, we report the biosynthetic gene cluster for pyracrimycin A, a set of nine genes that includes a core nonribosomal peptide synthase () that utilizes serine and proline as precursors and a monooxygenase () that catalyzes Baeyer-Villiger oxidation. The cluster is similar to the one for brabantamide A; however, pyracrimycin A biosynthesis differs in that feeding experiments with isotope-labeled serine and proline suggest that a ring opening reaction takes place and a carbon is lost from serine downstream of the oxidation reaction.
View Article and Find Full Text PDFMicrobiol Resour Announc
August 2022
The actinomycete sp. strain Gö40/10 has the potential to produce a range of secondary metabolites, one of which is collinolactone, a compound with neuroprotective properties and potential for pharmaceutical applications. The genome was sequenced with Oxford Nanopore Technologies MinION and Illumina MiSeq systems and consists of a single 9,635,564-nucleotide linear chromosome.
View Article and Find Full Text PDFare well-known producers of a range of different secondary metabolites, including antibiotics and other bioactive compounds. Recently, it has been demonstrated that "silent" biosynthetic gene clusters (BGCs) can be activated by heterologously expressing transcriptional regulators from other BGCs. Here, we have activated a silent BGC in sp.
View Article and Find Full Text PDFWe report the sequencing, assembly, and annotation of the genome of sp. CA-230715, a potentially interesting producer of natural products. The genome of CA-230715 was sequenced using PacBio, Illumina, and Nanopore technologies.
View Article and Find Full Text PDFStreptomyces griseofuscus DSM 40191 is a fast growing Streptomyces strain that remains largely underexplored as a heterologous host. Here, we report the genome mining of S. griseofuscus, followed by the detailed exploration of its phenotype, including the production of native secondary metabolites and ability to utilise carbon, nitrogen, sulphur and phosphorus sources.
View Article and Find Full Text PDFCRISPR base editing is a powerful method to engineer bacterial genomes. However, it restricts editing to single-nucleotide substitutions. Here, to address this challenge, we adapt a CRISPR-Prime Editing-based, DSB-free, versatile, and single-nucleotide resolution genetic manipulation toolkit for prokaryotes.
View Article and Find Full Text PDFMicrobiol Resour Announc
July 2021
Here, we report the sequencing, assembly, and annotation of the genome of the rare actinobacterium sp. strain CA-103260. The genome of CA-103260 was sequenced using PacBio and Illumina technologies and it consists of a circular 11,609,901-bp chromosome.
View Article and Find Full Text PDFActinobacteria have been a rich source of novel, structurally complex natural products for many decades. Although the largest genus is , from which the majority of antibiotics in current and past clinical use were originally isolated, other less common genera also have the potential to produce a wealth of novel secondary metabolites. One example is the genus, which currently contains only five reported species.
View Article and Find Full Text PDFHere, we report the sequencing, assembly, and annotation of the genome of sp. strain CA-256286. The genome consists of a linear 7,726,360-nucleotide chromosome and a linear 466,817-nucleotide putative plasmid.
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