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Conversion of Natural Products from Renewable Resources in Pharmaceuticals by Cytochromes P450
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Giovanna Di Nardo, Gianfranco Gilardi
This mutant was expressed in Streptomyces lividans and whole-cell biocatalysis allowed the production of more than 2 mg/L of 1α,25-dihydroxy vitamin D3 (Hayashi et al., 2010). In this case, biocatalysis offered also the opportunity to obtain other unknown metabolites that can be very important for their pharmaceutical properties. The metabolites 1α,25(R),26- and 1α,25(S),26-trihydroxy vitamin D3 were found as products of this enzyme variant and they were found to have antiproliferative effects (Ishizuka et al., 1990).
The Genetics of the Frankia-Actinorhizal Symbiosis
Published in Peter M. Gresshoff, Molecular Biology of Symbiotic Nitrogen Fixation, 2018
Pascal Simonet, Philippe Normand, Ann M. Hirsch, Antoon D. L. Akkermans
However, there are certain difficulties with using derivatives of pFQ31 as cloning vectors. Introduction of derivatives of pFQ31 into ArI3 and strains which normally possess it as an indigenous plasmid could be hindered by incompatibility between the two plasmids. To overcome this problem, one could clone into other Frankia strains or other actinomycetes for which no plasmid or no plasmid incompatible with pFQ31 has been detected. However, when a pFQ31 derivative with an antibiotic marker was transformed into Streptomyces lividans, there was no success.135 Another approach is to cure strain ArI3 of its native plasmids. Plasmid curing has been achieved by a number of methods including heat treatment,148 treatment with chemical agents149 such as acridine or ethidium bromide, or by regenerating protoplasts.147 In the course of regenerating Frankia protoplasts, Normand et al.146 tested 17 ArI3 and 20 AcoN24d colonies derived from regenerated protoplasts from the presence of two genetic markers, plasmids, and various symbiotic properties. All of the regenerated colonies were still infective, forming nitrogen-fixing nodules on Alnus glutinosa seedlings. However, one of the ArI3 regenerants, designated LC2, had lost its two plasmids. Evidence for the loss of the plasmids was obtained by both agarose gel electrophoresis of in-situ lysed cells39 and hybridization with radioactive probes. For other regenerants, the plasmid copy number was found to be higher than in the parent ArI3 strain indicating that plasmid content is affected by the isolation and regeneration procedure or that plasmid copy number control was mutated by the treatment.
The force-from-lipid principle and its origin, a ‘what is true for E. coli is true for the elephant’ refrain
Published in Journal of Neurogenetics, 2022
What microbial electrophysiology?? There was no such thing 50 years ago and there is still little of it today. The Paramecium work might be a bit of historical curiosity, but microbiology and electrophysiology remain two separate disciplines with different subject matter, using different methods, asking different questions. There was also no common language: One may think that ‘Bordetella’ is an opera and the other one may think that ‘afterhyperpolarization’ is a typo. This segregation is regrettable because ion channels are widely used beyond the nervous system. Today, one finds recognizable ion-channel genes in the genomes of all plants, animals, and microbes but we know little the functions these channels serve. E.g. we learn how ions are filtered from the crystal structure of KcsA (Doyle et al., 1998) but don’t know (or care to know) what it does for its owner, the Gram-positive Streptomyces lividans.
An overview of lantibiotic biosynthetic machinery promiscuity and its impact on antimicrobial discovery
Published in Expert Opinion on Drug Discovery, 2020
Although a substantial amount of expression and heterologous production work described to date has been focused upon Nisin and the NisBTC system it is worth noting a number of other modification systems have been utilized in the production of lantibiotics, these include the production of cinnamycin by transfer of the cin cluster into Streptomyces lividans 1326 [53], production of planosporicin by transferring the planosporicin biosynthetic cluster PspBCT into Nonomuraea sp [54]., production of lichenicidin A1 and A2 in E. coli by the incorporation of BliM1M2 and BliTP biosynthetic genes. In another example, SpaBTC which is involved in the production of lantibiotic subtilin has been used in B. subtilis for the expression of a nisin-subtilin combined lantibiotic [55].
The potential of gene therapy for mucopolysaccharidosis type I
Published in Expert Opinion on Orphan Drugs, 2020
Luisa Natalia Pimentel Vera, Guilherme Baldo
Another studied strategy was the use of a serine recombinase from the phage Streptomyces lividans., PhiC31 integrase, which is somewhat similar to transposons. It integrates a donor gene tagged with attB-enhancers sequence into pseudo-attP sites present in the mammalian genome [68]. Adding this recombinase to a vector carrying the IDUA transgene given by hydrodynamic injection into MPS I mice resulted in a high level of enzyme activity (over a 1000 U/ml) in blood. Unfortunately, this activity drops fast [68].