The dabABC operon is a marker of C4-alkylated monobactam biosynthesis and responsible for (2S,3R)-diaminobutyrate production
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ABSTRACT:
SUBMITTER: Li R
PROVIDER: S-EPMC10906522 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
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Project description:BackgroundSublancin is a novel and distinct antimicrobial glycopeptide that can be used as an alternative to conventional antibiotics. The reported production of sublancin by Bacillus subtilis 168 is poor because transcriptional regulatory circuit of sunA, a gene that encodes presublancin, is complex and difficult to control.ResultsA strong inducible and easy to control vegetative σA promoter of Pglv was introduced to replace that of sunA in situ in B. subtilis 1A747 [SPβc, prototroph, the derivative of B. subtilis 168 (trpC2)]. Meanwhile, other two strong promoters of P43 and PluxS were respectively placed before sunI and sunT-bdbA-sunS-bdbB, encoding five functional proteins that involved in the biosynthesis of mature sublancin. 642 mg sublancin was obtained from 1 L culture supernatant of recombinant B. subtilis 1A747 strains. Analysises of electrospray ionization mass spectrometry and circular dichroism spectrum showed that mature sublancin had a molecular weight of 3877.642 Da and displayed a α-helical conformation that are consistent with reported results. In addition, the mature sublancin was proved to be a potent antimicrobial glycopeptide with broad activity spectrum, moderate cytotoxicity and good conditional stability under high temperature, extreme pH and protease-rich environments, thus showing its potential for clinical applications.ConclusionsOur present findings suggest that recombinant B. subtilis 1A747 strains can effectively and efficiently biosynthesize mature sublancin. The replacement of native promoters provides an extra method for production improvement of some other complicated peptides such as nisin and subtilin.
| S-EPMC4336743 | biostudies-literature
Project description:Plasmalogens are vinyl ether-containing lipids produced by mammals and bacteria. The aerobic biosynthetic pathway in eukaryotes and bacteria is known, but the anaerobic pathway has remained a mystery. Here, we describe a two-gene operon (plasmalogen synthase, pls) responsible for plasmalogen production in the anaerobic bacterium Clostridium perfringens. While aerobic plasmalogen biosynthesis involves an oxidative conversion of an ether to a vinyl ether, anaerobic plasmalogen biosynthesis uses the reductive conversion of an ester to an aldehyde equivalent. Heterologous expression of the C. perfringens pls operon in E. coli conferred the ability to produce plasmalogens. The pls operon is predicted to encode a multidomain complex similar to benzoyl-CoA reductase/hydroxylacyl-CoA dehydratase (BCR/HAD) enzymes. Versions of this operon can be found in a wide range of obligate and facultative anaerobic bacteria, including many human gut microbes.
| S-EPMC7812594 | biostudies-literature
Project description:The yeast Saccharomyces cerevisiae is able to use para-aminobenzoic acid (pABA) in addition to 4-hydroxybenzoic acid as a precursor of coenzyme Q, a redox lipid essential to the function of the mitochondrial respiratory chain. The biosynthesis of coenzyme Q from pABA requires a deamination reaction at position C4 of the benzene ring to substitute the amino group with an hydroxyl group. We show here that the FAD-dependent monooxygenase Coq6, which is known to hydroxylate position C5, also deaminates position C4 in a reaction implicating molecular oxygen, as demonstrated with labeling experiments. We identify mutations in Coq6 that abrogate the C4-deamination activity, whereas preserving the C5-hydroxylation activity. Several results support that the deletion of Coq9 impacts Coq6, thus explaining the C4-deamination defect observed in Δcoq9 cells. The vast majority of flavin monooxygenases catalyze hydroxylation reactions on a single position of their substrate. Coq6 is thus a rare example of a flavin monooxygenase that is able to act on two different carbon atoms of its C4-aminated substrate, allowing its deamination and ultimately its conversion into coenzyme Q by the other proteins constituting the coenzyme Q biosynthetic pathway.
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Project description:The crystal structure of the title compound, C(6)H(11)NO(5), establishes the relative configuration at the four stereogenic centres; the absolute configuration is determined by the use of d-glucuronolactone as the starting material for the synthesis. Mol-ecules are linked by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds into a three-dimensional network, with each mol-ecule acting as a donor and acceptor for five hydrogen bonds.
| S-EPMC2970405 | biostudies-literature
Project description:Fenugreek is a dietary supplement for anti-aging and human health. (2S,3R,4S)-4-hydroxyisoleucine (4-HIL), which is extracted from fenugreek seeds, is expected to be a promising orally active drug for diabetes and diabetic nephropathy because of its insulinotropic effect. Although several chemical synthesis methods of 4-HIL have been proposed, these methods require multistep reactions to control the stereochemistry of 4-HIL. In this study, we modified the key enzyme 4-HIL dehydrogenase (HILDH) to overcome the biggest limitation in commercial-scale production of 4-HIL. As a result, an effective one-step carbonyl reduction to produce (2S,3R,4S)-4-HIL was successfully accomplished with strict stereoselectivity (>99% de). Mass production of (2S,3R,4S)-4-HIL by our synthetic method could have a significant contribution to the prevention of diabetes, dyslipidemia, and Alzheimer's disease. (120 words/200 words).
| S-EPMC5651801 | biostudies-literature
Project description:The absolute configuration has been determined for the title compound, C(14)H(20)N(2)OS. Inter-molecular N-H⋯O hydrogen bonds are observed in the crystal packing, forming infinitive one-dimensional chains with the base vector [100].
| S-EPMC2971194 | biostudies-literature
Project description:The N-sulfonated monobactams harbor considerable potential to combat emerging bacterial infections that are problematic to treat due to their metallo-β-lactamase mediated resistance against conventional β-lactam antibiotics. Herein, we report a divergent synthesis of C3-substituted 2,3-diaminopropionates featuring an array of small functional groups and examine their potential as alternative precursors during monobactam biosynthesis in a mutant strain (ΔsulG) of Pseudomonas acidophila that is deficient in the supply of this native precursor. In vitro assays revealed high diastereoselectivity, as well as a substrate tolerance by the terminal adenylation domain of the non-ribosomal peptide synthetase (NRPS) SulM toward the majority of synthetic analogs. Chemical complementation of this mutant yielded a fluorinated, bioactive monobactam through fermentation as confirmed by a combination of spectrometric data and microbiological assays. This study demonstrates site-specific functionalization of a clinically important natural product and sets in place a platform for further strain improvements and engineered NRPS-biosynthesis of non-native congeners.
| S-EPMC10074443 | biostudies-literature
Project description:In the title mol-ecule, C15H12O3, the C atoms bearing the hy-droxy group and the phenyl ring are disordered over two sets of sites with refined occupancies of 0.573 (7) and 0.427 (7). There is also disorder of the phenyl ring but the hy-droxy group was refined as ordered. The dihedral angles between the benzene ring of the chromane ring system and the phenyl ring are 89.7 (2)° for the major component of disorder and 72.1 (3)° for the minor component. Both disorder components of the the di-hydro-pyran ring are in a half-chair conformation. In the crystal, mol-ecules are linked by pairs of O-H⋯O hydrogen bonds, forming inversion dimers with an R 2 (2)(10) graph-set motif. Weak C-H⋯π inter-actions link these dimers into ladders along [001].
| S-EPMC4384603 | biostudies-literature
Project description:To maintain the turgor pressure of the cell under high osmolarity, bacteria accumulate small organic compounds called compatible solutes, either through uptake or biosynthesis. Vibrio parahaemolyticus, a marine halophile and an important human and shellfish pathogen, has to adapt to abiotic stresses such as changing salinity. Vibrio parahaemolyticus contains multiple compatible solute biosynthesis and transporter systems, including the ectABC-asp_ect operon required for de novo ectoine biosynthesis. Ectoine biosynthesis genes are present in many halotolerant bacteria; however, little is known about the mechanism of regulation. We investigated the role of the quorum sensing master regulators OpaR and AphA in ect gene regulation. In an opaR deletion mutant, transcriptional reporter assays demonstrated that ect expression was induced. In an electrophoretic mobility shift assay, we showed that purified OpaR bound to the ect regulatory region indicating direct regulation by OpaR. In an aphA deletion mutant, expression of the ect genes was repressed, and purified AphA bound upstream of the ect genes. These data indicate that AphA is a direct positive regulator. CosR, a Mar-type regulator known to repress ect expression in V. cholerae, was found to repress ect expression in V. parahaemolyticus In addition, we identified a feed-forward loop in which OpaR is a direct activator of cosR, while AphA is an indirect activator of cosR Regulation of the ectoine biosynthesis pathway via this feed-forward loop allows for precise control of ectoine biosynthesis genes throughout the growth cycle to maximize fitness.IMPORTANCE Accumulation of compatible solutes within the cell allows bacteria to maintain intracellular turgor pressure and prevent water efflux. De novo ectoine production is widespread among bacteria, and the ect operon encoding the biosynthetic enzymes is induced by increased salinity. Here, we demonstrate that the quorum sensing regulators AphA and OpaR integrate with the osmotic stress response pathway to control transcription of ectoine biosynthesis genes in V. parahaemolyticus We uncovered a feed-forward loop wherein quorum sensing regulators also control transcription of cosR, which encodes a negative regulator of the ect operon. Moreover, our data suggest that this mechanism may be widespread in Vibrio species.
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Project description:The title compound, C(11)H(18)O(3), was synthesized to prove the relative configuration of the corresponding acyclic C1-C8 stereopentade. It crystallizes with two mol-ecules in the asymmetric unit, which show only slight differences. The mol-ecules are linked via O-H⋯O hydrogen bonds, resulting in two crystallographically independent chains of mol-ecules propagating in the a-axis direction. The absolute configuration was known from the synthesis.
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