-
Natural Product Reports Jun 2024Covering: 2017.01 to 2023.11Natural products biosynthesized by myxobacteria are appealing due to their sophisticated chemical skeletons, remarkable biological... (Review)
Review
Covering: 2017.01 to 2023.11Natural products biosynthesized by myxobacteria are appealing due to their sophisticated chemical skeletons, remarkable biological activities, and intriguing biosynthetic enzymology. This review aims to systematically summarize the advances in the discovery methods, new structures, and bioactivities of myxobacterial NPs reported in the period of 2017-2023. In addition, the peculiar biosynthetic pathways of several structural families are also highlighted.
Topics: Biological Products; Myxococcales; Molecular Structure; Biosynthetic Pathways; Drug Discovery
PubMed: 38390645
DOI: 10.1039/d3np00062a -
Sheng Wu Gong Cheng Xue Bao = Chinese... Sep 2003Novel macrolides epothilones, produced by cellulolytic myxobacterium Sorangium cellulosum, have the activity to promote microtubule assembly, and are considered to be a... (Review)
Review
Novel macrolides epothilones, produced by cellulolytic myxobacterium Sorangium cellulosum, have the activity to promote microtubule assembly, and are considered to be a potential successor to the famous antitumor drug taxol. The biosynthetic genes leading to the epothilones are clustered into a large operon. The multi-enzyme complex is a hetero-gene cluster of polyketide synthase (PKS) and non-ribosomal peptide synthetases (NRPS) and contains several functional modules, i.e. a loading module, one NRPS module, eight PKS modules, and a P450 epoxidase. The former ten modules biosynthesize desoxyepothilone (epothilones C and D), which is then epoxidized at C12 and C13 and converted into epothilones (epothilones A and B) by the P450 epoxidase. The NRPS module is responsible for the formation of the thiazole side chain from cysteine. The biosynthesis procedure of epothilones can be divided into 5 stages, i.e. formation of holo-ACP/PCP, chain initiation and thiazole ring formation, chain elongation, termination and epoxidation, and post-modification. The analysis of the gene cluster and the biosynthetic pathway reveals that novel epothilone analogs could not only be produced by chemical synthesis/modification, tranditional microbial technologies, but also can be genetically manipulated through combinatiorial biosynthesis approaches.
Topics: Bacterial Proteins; Epothilones; Molecular Structure; Multigene Family; Myxococcales; Peptide Synthases; Polyketide Synthases
PubMed: 15969075
DOI: No ID Found -
Molecules (Basel, Switzerland) Feb 2018Two new secondary metabolites, labindole A [2-methyl-3-(2-nitroethyl)-3H-indole] () and labindole B [2-methyl-3-(2-nitrovinyl)-3H-indole] (), were isolated from the...
Two new secondary metabolites, labindole A [2-methyl-3-(2-nitroethyl)-3H-indole] () and labindole B [2-methyl-3-(2-nitrovinyl)-3H-indole] (), were isolated from the myxobacterium (DSM 27648). Additionally, four metabolites , , and already known from other sources were obtained. Their structures were elucidated from high resolution electrospray ionisation mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR) spectroscopy data and their relative configuration was assigned based on nuclear Overhauser effect (NOE) and vicinal ¹H-NMR coupling data. The compounds where tested for biological activities; labindoles A () and B () exhibited significant activity against Hepatitis C Virus, 9-carbazole (), 3-chloro-9-carbazole () and 4-hydroxymethyl-quinoline () showed antifungal activities. Moreover, compound had weak to moderate antibacterial activities, while labindoles A () and B () were devoid of significant antifungal and antibacterial effects.
Topics: Anti-Infective Agents; Antiviral Agents; Biological Products; Fermentation; Hepacivirus; Heterocyclic Compounds; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Structure; Myxococcales; Secondary Metabolism
PubMed: 29495640
DOI: 10.3390/molecules23030542 -
Chemistry & Biology Jun 2006Considerable progress has been achieved in elucidating the biosynthesis of natural products with interesting cellular targets. In this issue of Chemistry & Biology,...
Considerable progress has been achieved in elucidating the biosynthesis of natural products with interesting cellular targets. In this issue of Chemistry & Biology, Rachid et al. provide a new example, taming genetic manipulation of the producer of chondramide, an actin-interfering compound.
Topics: Bacterial Proteins; Biological Products; Depsipeptides; Myxococcales
PubMed: 16793512
DOI: 10.1016/j.chembiol.2006.06.004 -
Journal of the American Chemical Society Dec 2004The antimitotic natural product disorazole C1 was isolated in 1994 from the fermentation broth of the myxobacterium Sorangium cellulosum. We have developed a highly...
The antimitotic natural product disorazole C1 was isolated in 1994 from the fermentation broth of the myxobacterium Sorangium cellulosum. We have developed a highly convergent and stereoselective total synthesis of this compound which establishes its relative and absolute configuration. Key features of our synthesis include a highly convergent strategy and selective functional group manipulations that minimize decomposition of the sensitive polyene macrodiolide.
Topics: Macrolides; Myxococcales; Oxazoles; Stereoisomerism
PubMed: 15563138
DOI: 10.1021/ja0443068 -
Current Biology : CB Jul 2007Many bacteria simultaneously grow and spread rapidly over a surface that supplies them with nutrient. Called 'swarming', this pattern of movement directs new cells to... (Review)
Review
Many bacteria simultaneously grow and spread rapidly over a surface that supplies them with nutrient. Called 'swarming', this pattern of movement directs new cells to the edge of the colony. Swarming reduces competition between cells for nutrients, speeding growth. Behind the swarm edge, where the cell density is higher, growth is limited by transport of nutrient from the subsurface to the overlying cells. Despite years of study, the choreography of swarm cell movement, the bacterial equivalent of dancing toward an exit in a very dense crowd of moving bodies, remains a mystery. Swarming can be propelled by rotating flagella, and either by pulling with type IV pili or by pushing with the secretion of slime. By identifying patterns of movement that are common to swarms making use of different engines, a model of swarm choreography can be proposed.
Topics: Bacteria; Bacterial Physiological Phenomena; Flagella; Locomotion; Models, Biological; Myxococcales
PubMed: 17637359
DOI: 10.1016/j.cub.2007.04.050 -
Journal of Natural Products Nov 2022Myxobacteria have proven to be a rich source of natural products, but their biosynthetic potential seems to be underexplored given the high number of biosynthetic gene...
Myxobacteria have proven to be a rich source of natural products, but their biosynthetic potential seems to be underexplored given the high number of biosynthetic gene clusters present in their genomes. In this study, a truncated ajudazol biosynthetic gene cluster in sp. SBCb004 was identified using mutagenesis and metabolomics analyses and a set of novel ajudazols (named ajudazols C-J, -, respectively) were detected and subsequently isolated. Their structures were elucidated using comprehensive HR-MS and NMR spectroscopy. Unlike the known ajudazols A () and B (), which utilize acetyl-CoA as the biosynthetic starter unit, these novel ajudazols were proposed to incorporate 3,3-dimethylacrylyl CoA as the starter. Ajudazols C-J (-, respectively) are characterized by varying degrees of hydroxylation, desaturation, and different glycosylation patterns. Two P450-dependent enzymes and one glycosyltransferase are shown to be responsible for the hydroxylation at C-8, the desaturation at C-15 and C-33, and the transfer of a d--glucopyranose, respectively, based on mutagenesis results. One of the cytochrome P450-dependent enzymes and the glycosyltransferase were found to be encoded by genes located outside the biosynthetic gene cluster. Ajudazols C-H (-, respectively) exhibit cytotoxicity against various cancer cell lines.
Topics: Cytotoxins; Glycosyltransferases; Multigene Family; Mutagenesis; Myxococcales; Genome, Bacterial
PubMed: 36331369
DOI: 10.1021/acs.jnatprod.2c00637 -
International Journal of Systematic and... Feb 2017A novel myxobacterium, strain MSr11462T, was isolated in 2015 from a soil sample collected form Kish Island beach, Persian Gulf, Iran. It displayed general myxobacterial...
A novel myxobacterium, strain MSr11462T, was isolated in 2015 from a soil sample collected form Kish Island beach, Persian Gulf, Iran. It displayed general myxobacterial features like Gram-negative staining, rod-shaped vegetative cells, gliding on solid surfaces, microbial lytic activity, fruiting-body-like aggregates and myxospore-like structures. The strain was mesophilic, aerobic and showed a chemoheterotrophic mode of nutrition. It was resistant to many antibiotics like gentamycin, polymyxin, fusidic acid and trimethoprim, and the key fatty acids of whole-cell hydrolysates were iso-C15 : 0, C16 : 0, iso-C17 : 0, C18 : 1, iso-C17 : 1 2-OH, C18 : 1 2-OH, iso-C15 : 0 OAG (O-alkylglycerol) and C16 : 1 OAG. The 16S rRNA gene sequence showed highest similarity (98.6 %) to Racemicystis crocea strain MSr9521T (GenBank accession no. KT591707). The phylogenetic analysis based on 16S rRNA gene sequences and matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) spectroscopy data supports a novel species of the family Polyangiaceae and the genus Racemicystis. DNA-DNA hybridization showed only about 50 % similarity between the novel strain and the phylogenetically closest species, Racemicystis. crocea MSr9521T. On the basis of a comprehensive taxonomic study, we propose a novel species, Racemicystis persica sp. nov., for strain MSr11462T (=DSM 103165T=NCCB 100606T).
Topics: Bacterial Typing Techniques; Base Composition; DNA, Bacterial; Fatty Acids; Iran; Islands; Myxococcales; Nucleic Acid Hybridization; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Soil Microbiology
PubMed: 27902273
DOI: 10.1099/ijsem.0.001655 -
Scientific Reports Feb 2021Considered a key taxon in soil and marine microbial communities, myxobacteria exist as coordinated swarms that utilize a combination of lytic enzymes and specialized...
Considered a key taxon in soil and marine microbial communities, myxobacteria exist as coordinated swarms that utilize a combination of lytic enzymes and specialized metabolites to facilitate predation of microbes. This capacity to produce specialized metabolites and the associated abundance of biosynthetic pathways contained within their genomes have motivated continued drug discovery efforts from myxobacteria. Of all myxobacterial biosynthetic gene clusters deposited in the antiSMASH database, only one putative acylhomoserine lactone (AHL) synthase, agpI, was observed, in genome data from Archangium gephyra. Without an AHL receptor also apparent in the genome of A. gephyra, we sought to determine if AgpI was an uncommon example of an orphaned AHL synthase. Herein we report the bioinformatic assessment of AgpI and discovery of a second AHL synthase from Vitiosangium sp. During axenic cultivation conditions, no detectible AHL metabolites were observed in A. gephyra extracts. However, heterologous expression of each synthase in Escherichia coli provided detectible quantities of 3 AHL signals including 2 known AHLs, C8-AHL and C9-AHL. These results suggest that A. gephyra AHL production is dormant during axenic cultivation. The functional, orphaned AHL synthase, AgpI, is unique to A. gephyra, and its utility to the predatory myxobacterium remains unknown.
Topics: Acyl-Butyrolactones; Escherichia coli; Ligases; Myxococcales; Phylogeny; Quorum Sensing; Sequence Analysis, DNA
PubMed: 33542315
DOI: 10.1038/s41598-021-82480-1 -
Current Opinion in Drug Discovery &... Mar 2009Myxobacteria produce an immense variety of natural products with useful biological activities. This review highlights recent advances to evaluate and further explore... (Review)
Review
Myxobacteria produce an immense variety of natural products with useful biological activities. This review highlights recent advances to evaluate and further explore their biosynthetic potential for drug discovery, with particular focus on polyketide synthase and non-ribosomal peptide synthetase-derived secondary metabolites.
Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Biological Products; Drug Discovery; Gene Expression Regulation, Bacterial; Gene Regulatory Networks; Humans; Myxococcales; Peptide Synthases; Polyketide Synthases; Structure-Activity Relationship
PubMed: 19333867
DOI: No ID Found