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Production of OTC by industrial strains M4018 and R6-500 and engineered strains with 145 and 240 kb deletion compared to the parent strain S. rimosus ATCC 10970. Mean with error bars showing s.d. (n = 9, three independent fermentations from three biological replicates). Significance is tested with Dunnett’s T3-test, ****P < 0.0001.
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Most biosynthetic gene clusters (BGC) encoding the synthesis of important microbial secondary metabolites, such as antibiotics, are either silent or poorly expressed; therefore, to ensure a strong pipeline of novel antibiotics, there is a need to develop rapid and efficient strain development approaches. This study uses comparative genome analysis...
Citations
... Here, inspired by the previously reported results, we conducted the cultivations of a biotechnologically relevant filamentous fungal species of remarkably rich SM catalogue (Amr et al. 2023;Boruta and Bizukojć 2016;Guo and Wang 2014), namely Aspergillus terreus (the producer of lovastatin, a cholesterol-lowering drug), to describe its morphology and SM repertoire at pH values between 2 and 6, i.e., within the pH range expected to yield a diverse spectrum of morphological forms. For comparative purposes, the cultures of a model actinomycete (Pšeničnik et al. 2024) Streptomyces rimosus (the producer of oxytetracycline, a broad-spectrum antibiotic) were investigated in parallel with A. terreus cultures. To the best of our knowledge, the SM landscapes of A. terreus and S. rimosus have never been investigated in relation to the pH-dependent morphological diversity. ...
The influence of the initial pH on the morphology and secondary metabolite production in cocultures and axenic cultures of Aspergillus terreus and Streptomyces rimosus was investigated. The detected secondary metabolites (6 of bacterial and 4 of fungal origin) were not found in the cultures initiated at pH values less than or equal to 4.0. The highest mean levels of oxytetracycline were recorded in S. rimosus axenic culture at pH 5.0. Initiating the axenic culture at pH 5.9 led to visibly lower product levels, yet the presence of A. terreus reduced the negative effect of non-optimal pH and led to higher oxytetracycline titer than in the corresponding S. rimosus axenic culture. The cocultivation initiated at pH 5.0 or 5.9 triggered the formation of oxidized rimocidin. The products of A. terreus were absent in the cocultures. At pH 4.0, the striking morphological differences between the coculture and the axenic cultures were recorded.
... In an effort to validate for molecule production, gene deletions or knockouts have been proposed using homologous recombination from the genomes of source organisms (Netzker et al. 2016). In genetic engineering, targeted genome reductions have also proven useful for the enhancement of metabolite production in Streptomyces (Pšeničnik et al. 2024). ...
Streptomyces has long been considered as key sources for natural compounds discovery in medicine and agriculture. These compounds have been demonstrated to possess different biological activities, including antibiotic, antifungal, anticancer, and antiviral effects. As a result, new pharmaceuticals and antibiotics have been developed. Nevertheless, there have been only a few novel discoveries of bioactive compounds in the past decades from Streptomyces in natural habitats. There is, therefore, now a renewed search for new Streptomyces species having the potential to produce many compounds from one strain in lesser explored natural habitats that may be helpful in fighting diseases. Consequently, modern genome mining approaches are imperative for discovering structurally novel natural compounds with therapeutic applications from untapped sources. In light of these facts, endophytic Streptomyces from plants may offer new avenues for the discovery of bioactive compounds with distinctive chemical properties and activities. In the present review, we present the progress made in isolating natural compounds from endophytic Streptomyces originating from plants which have remarkable antimicrobial, cytotoxic, and antifungal properties. A different of distinct structural classes of compounds were reported from endophytic Streptomyces, such as indolosequiterpene, macrolides, flavones, peptides, naphthoquinones, and terpenoids. Further, we discussed modern genomics progress in finding biosynthetic gene clusters (BGCs) encoding compounds. Overall, this review might provide valuable insights into the potential for novel drug discovery from untapped endophytic Streptomyces in the future.
The development of sustainable processes is the most important basis to realize the shift from the fossil-fuel based industry to bio-based production. Non-model microbes represent a great resource due to their advantageous traits and unique repertoire of bioproducts. However, most of these microbes require modifications to improve their growth and production capacities as well as robustness in terms of genetic stability. For this, genome reduction is a valuable and powerful approach to meet industry requirements and to design highly efficient production strains. Here, we provide an overview of various genome reduction approaches in prokaryotic microorganisms, with a focus on non-model organisms, and highlight the example of a successful genome-reduced model organism chassis. Furthermore, we discuss the advances and challenges of promising non-model microbial chassis.
