Fungal 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 PDFThe candidate phyla radiation (CPR) represents a distinct monophyletic clade and constitutes a major portion of the tree of life. Extensive efforts have focused on deciphering the functional diversity of its members, primarily using sequencing-based techniques. However, cultivation success remains scarce, presenting a significant challenge, particularly in CPR-dominated groundwater microbiomes characterized by low biomass.
View Article and Find Full Text PDFTrends Biotechnol
August 2024
Microbial electrosynthesis (MES) is an emerging technology that couples renewable electricity to microbial production processes. Although advances in MES performance have been driven largely by microbial mixed cultures, we see a great limitation in the diversity, and hence value, of products that can be achieved in undefined mixed cultures. By contrast, metabolic control of pure cultures and genetic engineering could greatly expand the scope of MES, and even of broader electrobiotechnology, to include targeted high-value products.
View Article and Find Full Text PDFPseudomonas aeruginosa phenazines contribute to survival under microaerobic and anaerobic conditions by extracellular electron discharge to regulate cellular redox balances. This electron discharge is also attractive to be used for bioelectrochemical applications. However, elements of the respiratory pathways that interact with phenazines are not well understood.
View Article and Find Full Text PDFNonribosomal peptide synthetases (NRPSs) are giant enzymatic assembly lines that deliver many pharmaceutically valuable natural products, including antibiotics. As the search for new antibiotics motivates attempts to redesign nonribosomal metabolic pathways, more robust and rapid sorting and screening platforms are needed. Here, we establish a microfluidic platform that reliably detects production of the model nonribosomal peptide gramicidin S.
View Article and Find Full Text PDFMicrobial electrosynthesis (MES) is a very promising technology addressing the challenge of carbon dioxide recycling into organic compounds, which might serve as building blocks for the (bio)chemical industry. However, poor process control and understanding of fundamental aspects such as the microbial extracellular electron transfer (EET) currently limit further developments. In the model acetogen , both direct and indirect electron consumption hydrogen have been proposed.
View Article and Find Full Text PDFBecause of its high sensitivity to even small objects and the quick measurement principle, angle-resolved scattering (ARS) measurements exhibit a promising potential as a rapid analysis tool for bacterial cells at small sample sizes and very low numbers of cells. In this study, investigations on scattered light from various bacterial cell samples revealed applicability down to single cell levels, which is a huge benefit compared to conventional methods that depend on time-consuming cellular growth over several hours or even days. With the proposed setup and data analysis method, it is possible to detect scatter differences among cell types, together with the cell concentration.
View Article and Find Full Text PDFspecies are intensively studied for their ability to produce a variety of natural products. However, conditions influencing and leading to product formation are often not completely recognized. Therefore, in this study, high-throughput online monitoring is presented as a powerful tool to gain in-depth understanding of the cultivation of the model organism A3(2).
View Article and Find Full Text PDFMediated extracellular electron transfer (EET) might be a great vehicle to connect microbial bioprocesses with electrochemical control in stirred-tank bioreactors. However, mediated electron transfer to date is not only much less efficient but also much less studied than microbial direct electron transfer to an anode. For example, despite the widespread capacity of pseudomonads to produce phenazine natural products, only Pseudomonas aeruginosa has been studied for its use of phenazines in bioelectrochemical applications.
View Article and Find Full Text PDFMicrobial cocultures are used as a tool to stimulate natural product biosynthesis. However, studies often empirically combine different organisms without a deeper understanding of the population dynamics. As filamentous organisms offer a vast metabolic diversity, we developed a model filamentous coculture of the cellulolytic fungus Trichoderma reesei RUT-C30 and the noncellulolytic bacterium Streptomyces coelicolor A3(2).
View Article and Find Full Text PDFMicrobial electrosynthesis (MES) from CO provides chemicals and fuels by driving the metabolism of microorganisms with electrons from cathodes in bioelectrochemical systems. These microorganisms are usually strictly anaerobic. At the same time, the anode reaction of bioelectrochemical systems is almost exclusively water splitting through the oxygen evolution reaction (OER).
View Article and Find Full Text PDFUnderstanding population dynamics is a key factor for optimizing co-culture processes to produce valuable compounds. However, the measurement of independent population dynamics is difficult, especially for filamentous organisms and in presence of insoluble substrates like cellulose. We propose a workflow for fluorescence-based online monitoring of individual population dynamics of two filamentous microorganisms.
View Article and Find Full Text PDFThe market of biobased products obtainable via fermentation processes has steadily increased over the past few years, driven by the need to create a decarbonized economy. To date, industrial fermentation (IF) employs either pure or mixed microbial cultures (MMC), whereby the type of the microbial catalysts and the used feedstock affect metabolic pathways and, in turn, the type of product(s) generated. In many cases, especially when dealing with MMC, the economic viability of IF is still hindered by factors such as the low attained product titer and selectivity, which ultimately challenge the downstream recovery and purification steps.
View Article and Find Full Text PDFElectroactive microorganisms can exchange electrons with other cells or conductive interfaces in their extracellular environment. This property opens the way to a broad range of practical biotechnological applications, from manufacturing sustainable chemicals via electrosynthesis, to bioenergy, bioelectronics or improved, low-energy demanding wastewater treatments. Besides, electroactive microorganisms play key roles in environmental bioremediation, significantly impacting process efficiencies.
View Article and Find Full Text PDFDroplet microfluidics offers a unique opportunity for ultrahigh-throughput experimentation with minimal sample consumption and thus has obtained increasing attention, particularly for biological applications. Detection and measurements of analytes or biomarkers in tiny droplets are essential for proper analysis of biological and chemical assays like single-cell studies, cytometry, nucleic acid detection, protein quantification, environmental monitoring, drug discovery, and point-of-care diagnostics. Current detection setups widely use microscopes as a central device and other free-space optical components.
View Article and Find Full Text PDFCyclic lipopeptides are substances with a high potential to act as antimicrobial agents. Jagaricin, produced by DSM 9628 and discovered in 2012, is a new member of this class with promising antifungal properties. However, further experiments to investigate future applications and/or conduct chemical derivatization to change properties and toxicity are impossible due to the limited access to jagaricin.
View Article and Find Full Text PDFIn today's, society multi-resistant pathogens have become an emerging threat, which makes the search for novel anti-infectives more urgent than ever. A promising class of substances are cyclic lipopeptides like the antifungal jagaricin. Jagaricin is formed by the bacterial mushroom pathogen Janthinobacterium agaricidamnosum.
View Article and Find Full Text PDFPseudomonas aeruginosa produces phenazine-1-carboxylic acid (PCA) and pyocyanin (PYO), which aid its anaerobic survival by mediating electron transfer to distant oxygen. These natural secondary metabolites are being explored in biotechnology to mediate electron transfer to the anode of bioelectrochemical systems. A major challenge is that only a small fraction of electrons from microbial substrate conversion is recovered.
View Article and Find Full Text PDFAntibiotics from few culturable microorganisms have saved millions of lives since the 20th century. But with resistance formation, these compounds become increasingly ineffective, while the majority of microbial and with that chemical compound diversity remains inaccessible for cultivation and exploration. Culturing recalcitrant bacteria is a stochastic process.
View Article and Find Full Text PDFMicrobial mixed cultures are gaining increasing attention as biotechnological production systems, since they offer a large but untapped potential for future bioprocesses. Effects of secondary metabolite induction and advantages of labor division for the degradation of complex substrates offer new possibilities for process intensification. However, mixed cultures are highly complex, and, consequently, many biotic and abiotic parameters are required to be identified, characterized, and ideally controlled to establish a stable bioprocess.
View Article and Find Full Text PDFThe isolation and sequencing of new strains of Pseudomonas aeruginosa created an extensive dataset of closed genomes. Many of the publicly available genomes are only used in their original publication while additional in silico information, based on comparison to previously published genomes, is not being explored. In this study, we defined and investigated the genome of the environmental isolate P.
View Article and Find Full Text PDFSufficient supply of oxygen is a major bottleneck in industrial biotechnological synthesis. One example is the heterologous production of rhamnolipids using KT2440. Typically, the synthesis is accompanied by strong foam formation in the reactor vessel hampering the process.
View Article and Find Full Text PDFBackground: Itaconic acid is a bio-derived platform chemical with uses ranging from polymer synthesis to biofuel production. The efficient conversion of cellulosic waste streams into itaconic acid could thus enable the sustainable production of a variety of substitutes for fossil oil based products. However, the realization of such a process is currently hindered by an expensive conversion of cellulose into fermentable sugars.
View Article and Find Full Text PDFACS Chem Biol
December 2020
Microbial phenazines are getting increasing attention for antimicrobial and biotechnological applications. Phenazine production of the most well-known producer is subject to a highly complex regulation network involving both quorum sensing and catabolite repression. These networks affect the expression of the two redundant gene operons responsible for phenazine-1-carboxylate (PCA) production and two specific genes and necessary for pyocyanin production.
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