The biosynthesis of streptomycin. The origin of the C-formyl group of streptose.
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ABSTRACT:
SUBMITTER: Candy DJ
PROVIDER: S-EPMC1207070 | biostudies-other | 1965 Aug
REPOSITORIES: biostudies-other
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Project description:FK506 (tacrolimus) is a secondary metabolite with a potent immunosuppressive activity, currently registered for use as immunosuppressant after organ transplantation. FK506 and FK520 are biogenetically related natural products that are synthesized by combined polyketide synthase/nonribosomal peptide synthetase systems. The entire gene cluster for biosynthesis of FK520 from Streptomyces hygroscopicus var. ascomyceticus has been cloned and sequenced. On the other hand, the FK506 gene cluster from Streptomyces sp. MA6548 (ATCC55098) was sequenced only partially, and it was reasonable to expect that additional genes would be required for the provision of substrate supply. Here we report the identification of a previously unknown region of the FK506 gene cluster from Streptomyces tsukubaensis NRRL 18488 containing genes encoding the provision of unusual building blocks for FK506 biosynthesis as well as a regulatory gene. Among others, we identified a group of genes encoding biosynthesis of the extender unit that forms the allyl group at carbon 21 of FK506. Interestingly, we have identified a small independent diketide synthase system involved in the biosynthesis of the allyl group. Inactivation of one of these genes, encoding an unusual ketosynthase domain, resulted in an FK506 nonproducing strain, and the production was restored when a synthetic analog of the allylmalonyl-CoA extender unit was added to the cultivation medium. Based on our results, we propose a biosynthetic pathway for the provision of an unusual five-carbon extender unit, which is carried out by a novel diketide synthase complex.
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Project description:Green bacteria are chlorophotorophs that synthesize bacteriochlorophyll (BChl) c, d, or e, which assemble into supramolecular, nanotubular structures in large light-harvesting structures called chlorosomes. The biosynthetic pathways of these chlorophylls are known except for one reaction. Null mutants of bciD, which encodes a putative radical S-adenosyl-l-methionine (SAM) protein, are unable to synthesize BChl e but accumulate BChl c; however, it is unknown whether BciD is sufficient to convert BChl c (or its precursor, bacteriochlorophyllide (BChlide) c) into BChl e (or BChlide e). To determine the function of BciD, we expressed the bciD gene of Chlorobaculum limnaeum strain DSMZ 1677T in Escherichia coli and purified the enzyme under anoxic conditions. Electron paramagnetic resonance spectroscopy of BciD indicated that it contains a single [4Fe-4S] cluster. In assays containing SAM, BChlide c or d, and sodium dithionite, BciD catalyzed the conversion of SAM into 5'-deoxyadenosine and BChlide c or d into BChlide e or f, respectively. Our analyses also identified intermediates that are proposed to be 71-OH-BChlide c and d Thus, BciD is a radical SAM enzyme that converts the methyl group of BChlide c or d into the formyl group of BChlide e or f This probably occurs by a mechanism involving consecutive hydroxylation reactions of the C-7 methyl group to form a geminal diol intermediate, which spontaneously dehydrates to produce the final products, BChlide e or BChlide f The demonstration that BciD is sufficient to catalyze the conversion of BChlide c into BChlide e completes the biosynthetic pathways for all "Chlorobium chlorophylls."
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Project description:Origin and biosynthesis of coelenterazine
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Project description:Isoprenoids and their derivatives represent the largest group of organic compounds in nature and are distributed universally in the three domains of life. Isoprenoids are biosynthesized from isoprenyl diphosphate units, generated by two distinctive biosynthetic pathways: mevalonate pathway and methylerthritol 4-phosphate pathway. Archaea and eukaryotes exclusively have the former pathway, while most bacteria have the latter. Some bacteria, however, are known to possess the mevalonate pathway genes. Understanding the evolutionary history of these two isoprenoid biosynthesis pathways in each domain of life is critical since isoprenoids are so interweaved in the architecture of life that they would have had indispensable roles in the early evolution of life. Our study provides a detailed phylogenetic analysis of enzymes involved in the mevalonate pathway and sheds new light on its evolutionary history. The results suggest that a potential mevalonate pathway is present in the recently discovered superphylum Candidate Phyla Radiation (CPR), and further suggest a strong evolutionary relationship exists between archaea and CPR. Interestingly, CPR harbors the characteristics of both the bacterial-type and archaeal-type mevalonate pathways and may retain signatures regarding the ancestral isoprenoid biosynthesis pathway in the last universal common ancestor. Our study supports the ancient origin of the mevalonate pathway in the three domains of life as previously inferred, but concludes that the evolution of the mevalonate pathway was more complex.
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Project description:The bacterial division Synergistes represents a poorly characterized phylotype of which only a few isolates have been cultured, primarily from natural environments. Recent detection of Synergistes-like sequence types in periodontal pockets and caries lesions of humans prompted us to search the R. M. Alden culture collection (Santa Monica, Calif.) for biochemically unidentifiable, slow-growing, obligately anaerobic gram-negative bacilli. Here we report on five clinical isolates cultured from peritoneal fluid and two isolates from soft-tissue infections that together constitute three separate evolutionary lineages within the phylogenetic radiation of the division Synergistes. One of these clusters was formed by the peritoneal isolates and had an 85% similarity to Synergistes jonesii, the first described Synergistes species, which was isolated from the rumen of a goat. The isolates from soft-tissue infections, on the other hand, formed two distinct lineages moderately related to each other with a similarity of approximately 78%. In addition, by using a newly designed 16S rRNA gene-based PCR assay with intended target specificity for Synergistes, we found that the dominant phylotype from a fecal sample was nearly identical to that of the strains obtained from peritonitis. Conversely, sequence types detected in periodontal pockets formed a separate cluster that shared a similarity of only 80% with the soft-tissue isolates. These findings suggest a high diversity of medically important Synergistes clades that apparently are unique to individual ecological niches in the human body. In conclusion, we now have available the first characterized human isolates of the division Synergistes which are colonizing, and probably infecting, several sites in the human body.
| S-EPMC1594628 | biostudies-literature
Project description:Streptomycin sp. QHH-9511 genome sequencing
| PRJNA595049 | ENA
Project description:Carbon monoxide (CO) is an indispensable C1 building block. For decades this abundant gas has been employed in hydroformylation and Pausen-Khand catalysis, amongst many related chemistries, where a single, non-coupled CO fragment is delivered to an organic molecule. Despite this, organometallic species which react with CO to yield C1 products remain rare, and are elusive for main group metal complexes. Here, we describe a range of amido-beryllium hydride complexes, and demonstrate their reactivity towards CO, in its mono-insertion into the Be-H bonds of these species. The small radius of the Be2+ ion in conjunction with the non-innocent pendant phosphine moiety of the developed ligands leads to a unique beryllium formyl complex with an ylidic P-COC fragment, whereby the carbon centre, remarkably, datively binds Be. This, alongside reactivity toward carbon dioxide, sheds light on the insertion chemistry of the Be-H bond, complimenting the long-known chemistry of the heavier Alkaline Earth hydrides.
| S-EPMC8786820 | biostudies-literature
Project description:BackgroundLignin plays an important role in plant structural support and water transport, and is considered one of the hallmarks of land plants. The recent discovery of lignin or its precursors in various algae has raised questions on the evolution of its biosynthetic pathway, which could be much more ancient than previously thought. To determine the taxonomic distribution of the lignin biosynthesis genes, we screened all publicly available genomes of algae and their closest non-photosynthetic relatives, as well as representative land plants. We also performed phylogenetic analysis of these genes to decipher the evolution and origin(s) of lignin biosynthesis.ResultsEnzymes involved in making p-coumaryl alcohol, the simplest lignin monomer, are found in a variety of photosynthetic eukaryotes, including diatoms, dinoflagellates, haptophytes, cryptophytes as well as green and red algae. Phylogenetic analysis of these enzymes suggests that they are ancient and spread to some secondarily photosynthetic lineages when they acquired red and/or green algal endosymbionts. In some cases, one or more of these enzymes was likely acquired through lateral gene transfer (LGT) from bacteria.ConclusionsGenes associated with p-coumaryl alcohol biosynthesis are likely to have evolved long before the transition of photosynthetic eukaryotes to land. The original function of this lignin precursor is therefore unlikely to have been related to water transport. We suggest that it participates in the biological defense of some unicellular and multicellular algae.
| S-EPMC4455696 | biostudies-literature
Project description:Three new isomeric asymmetric diarylethenes with a naphthyl moiety and a formyl group at the para, meta or ortho position of the terminal benzene ring were synthesized. Their photochromism, fluorescent-switch, and electrochemical properties were investigated. Among these diarylethenes, the one with a formyl group at the ortho position of benzene displayed the largest molar absorption coefficients and fluorescence quantum yield. The cyclization quantum yields of these compounds increased in the order of para < ortho < meta, whereas their cycloreversion quantum yields decreased in the order of meta > para > ortho. Additionally, all of these diarylethenes functioned as effective fluorescent switches in both solution and PMMA films. Cyclic voltammograms proved that the formyl group and its position could effectively modulate the electrochemical behaviors of these diarylethene derivatives.
| S-EPMC3458719 | biostudies-literature
Project description:BackgroundCaprazamycins are liponucleoside antibiotics showing bioactivity against Gram-positive bacteria including clinically relevant Mycobacterium tuberculosis by targeting the bacterial MraY-translocase. Their chemical structure contains a unique 3-methylglutaryl moiety which they only share with the closely related liposidomycins. Although the biosynthesis of caprazamycin is understood to some extent, the origin of 3-methylglutaryl-CoA for caprazamycin biosynthesis remains elusive.ResultsIn this work, we demonstrate two pathways of the heterologous producer Streptomyces coelicolor M1154 capable of supplying 3-methylglutaryl-CoA: One is encoded by the caprazamycin gene cluster itself including the 3-hydroxy-3-methylglutaryl-CoA synthase Cpz5. The second pathway is part of primary metabolism of the host cell and encodes for the leucine/isovalerate utilization pathway (Liu-pathway). We could identify the liu cluster in S. coelicolor M1154 and gene deletions showed that the intermediate 3-methylglutaconyl-CoA is used for 3-methylglutaryl-CoA biosynthesis. This is the first report of this intermediate being hijacked for secondary metabolite biosynthesis. Furthermore, Cpz20 and Cpz25 from the caprazamycin gene cluster were found to be part of a common route after both individual pathways are merged together.ConclusionsThe unique 3-methylglutaryl moiety in caprazamycin originates both from the caprazamycin gene cluster and the leucine/isovalerate utilization pathway of the heterologous host. Our study enhanced the knowledge on the caprazamycin biosynthesis and points out the importance of primary metabolism of the host cell for biosynthesis of natural products.
| S-EPMC9636800 | biostudies-literature