A bacterial cytidine deaminase toxin enables crispr-free mitochondrial base editing - understand
Weaver; Recent developments of tools for genome and metabolome studies in basidiomycete fungi and their application to natural product research. Biol Open 15 December ; 9 12 : bio Basidiomycota are a large and diverse phylum of fungi. They can make bioactive metabolites that are used or have inspired the synthesis of antibiotics and agrochemicals. Terpenoids are the most abundant class of natural products encountered in this taxon. Other natural product classes have been described, including polyketides, peptides, and indole alkaloids. The discovery and study of natural products made by basidiomycete fungi has so far been hampered by several factors, which include their slow growth and complex genome architecture. Recent developments of tools for genome and metabolome studies are allowing researchers to more easily tackle the secondary metabolome of basidiomycete fungi. Inexpensive long-read whole-genome sequencing enables the assembly of high-quality genomes, improving the scaffold upon which natural product gene clusters can be predicted. a bacterial cytidine deaminase toxin enables crispr-free mitochondrial base editing.Introduction
This is because, despite offering a competitive advantage to the producing organism, they are not essential for its survival. Historically, selected groups of organisms have been the main focus for NP discovery; one such group of organisms is actinomycete bacteria, from which a variety of bioactive NPs Fig. These NPs include the antibiotic daptomycin, isolated from Streptomyces roseosporus Debono et al. Gram-negative bacteria are another important reservoir for NPs of varying bioactivities, including antibiotics, such as teixobactin Fig.
Plants represent another large source of NPs Fig. Structures of NPs mentioned in this article produced by organisms other than basidiomycete fungi. View large Download slide Structures of NPs mentioned in this article produced by organisms other than basidiomycete fungi. Fungi are also a rich source of NPs, with NP discovery primarily focusing on species belonging to the phylum Ascomycota thus far. Various NPs from ascomycete fungi hold prominent roles in our daily lives Fig.
Fungi of the phylum Basidiomycota represent a rich source of NPs, often overlooked for several key reasons, such as their large and complex genome structures, as well as being difficult to work with, as a consequence of their slow growth rate compared with other fungi and bacteria. Due to this, secondary metabolite study has lagged behind in basidiomycete fungi. Check this out the release of an increasing number of whole-genome sequences at present, more than basidiomycete genomes are accessible from the web portal of the US Department of Energy Joint Genome Instituteas well as their antiquity in a bacterial cytidine deaminase toxin enables crispr-free mitochondrial base editing medicine and a bacterial cytidine deaminase toxin enables crispr-free mitochondrial base editing usage, the interest in the study of NPs in basidiomycete fungi has grown considerably in recent years.
As commonly seen in other microorganisms, and to some extent in plants, the genes that code for fungal NP biosynthetic enzymes are often clustered together on the same genomic region, a feature that allows researchers to more easily mine the genetic determinants of NP biosynthesis Osbourn, Biosynthetic gene clusters can include genes coding for synthase enzymes, tailoring enzymes and transcriptional regulators Medema et al. Basidiomycete fungi and their NPs Fungi belonging to the phylum Basidiomycota can produce NPs that belong to several different biosynthetic classes Lin et al.
Each class of NPs are structurally diverse and encompass their own biosynthetic enzymatic machinery and tailoring enzymes. Interclass differences may also be vast, with individual metabolites varying in structure, bioactivity, and size. Terpenoids Terpenoids Fig. Opatz et al. A particularly important example of a bioactive terpenoid made by basidiomycete fungi is that of the antibiotic pleuromutilin, a diterpene antibacterial NP, initially discovered in the two fungi Pleurotus mutilus synonymous to Clitopilus scyphoides f. Pleuromutilin mediates its antibacterial bioactivity by inhibition of protein synthesis through selective binding at the peptidyl transferase centre, at the A- and P-sites of the ribosome Davidovich et al. Since its discovery, semi-synthetic derivatives tiamulin and valnemulin have been employed in veterinary use, and retapamulin is utilised as a topical antibiotic in humans Daum et al.
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More recently, lefamulin has been granted permission by the US FDA for use in the treatment of community-acquired bacterial pneumonia, becoming the first ever antibiotic derived from basidiomycete fungi to be approved for systemic use in humans Watkins and File, Structures of NPs mentioned in this article produced by basidiomycete fungi. View large Download slide Structures of NPs mentioned in this article produced by basidiomycete fungi. Terpenoids all consist of several isoprene units, however, diversification in structure can be achieved by differences in linearity or cyclicity, saturated or unsaturated bonds, and other modifications, such as reduction, decarboxylation, glycosylation, alkylation, and acetylation, to name a few. For details on the biosynthesis of fungal a bacterial cytidine deaminase toxin enables crispr-free mitochondrial base editing we refer the reader to other reviews on this topic Hoffmeister and Keller, ; Schmidt-Dannert, Polyketides PKs PKs are known to be poets jazz age abundant in fungi, with research primarily focusing on ascomycete fungi thus far.
Despite this, known PKs of basidiomycete fungi are structurally and functionally diverse Fig. Some examples of PKs produced by fungi of the phylum Basidiomycota include the antioxidant anthraquinone-related pigments, such as rufoolivacins, isolated from Cortinarius purpurascens Bai et al. For an overview of the biosynthetic mechanism of fungal PKs we refer the reader to other reviews on this topic Cox, ; Hoffmeister and Keller, Some NRPs found in fungi of the phylum Basidiomycota include ferrichrome and ferrichrome A, siderophores produced by Ustilago maydis Winterberg et al. Ribosomally synthesised and post-translationally modified peptides RiPPs Peptide NPs can be synthesised by two mechanisms.
Introduction
One is by the previously mentioned NRPSs, and another is ribosomally-driven synthesis. Unlike NRP synthesis, ribosomal biosynthesis requires the translation of a precursor peptide which must then be post-translationally modified, yielding the mature peptide. Fungal RiPPs Fig. Omphalotin A is a potent nematicidal cyclic dodecapeptide isolated from the jack-o'-lantern mushroom O. Commonly between RiPPs and other NPs is that their biosynthetic pathways are encoded by gene clusters. Indole alkaloids Indole alkaloids are one of the largest classes of nitrogen-containing secondary metabolites and are found across all kingdoms of life, however, fungi, particularly ascomycetes, are reportedly prolific producers of these NPs. Indole alkaloids are also well known in basidiomycete fungi Fig.]
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