A Widespread Radical-Mediated Glycolysis Pathway.

Glycyl radical enzymes (GREs) catalyze mechanistically diverse radical-mediated reactions, playing important roles in the metabolism of anaerobic bacteria. The model bacterium Escherichia coli MG1655 contains two GREs of unknown function, YbiW and PflD, which are widespread among human intestinal bacteria. Here, we report that YbiW and PflD catalyze ring-opening C-O cleavage of 1,5-anhydroglucitol-6-phosphate (AG6P) and 1,5-anhydromannitol-6-phosphate (AM6P), respectively. The product of both enzymes, 1-deoxy-fructose-6-phosphate (DF6P), is then cleaved by the aldolases FsaA or FsaB to form glyceraldehyde-3-phosphate (G3P) and hydroxyacetone (HA), which are then reduced by the NADH-dependent dehydrogenase GldA to form 1,2-propanediol (1,2-PDO). Crystal structures of YbiW and PflD in complex with their substrates provided insights into the mechanism of radical-mediated C-O cleavage. This "anhydroglycolysis" pathway enables anaerobic growth of E. coli on 1,5-anhydroglucitol (AG) and 1,5-anhydromannitol (AM), and we probe the feasibility of harnessing this pathway for the production of 1,2-PDO, a highly demanded chiral chemical feedstock, from inexpensive starch. Discovery of the anhydroglycolysis pathway expands the known catalytic repertoire of GREs, clarifies the hitherto unknown physiological functions of the well-studied enzymes FsaA, FsaB, and GldA, and demonstrates how enzyme discovery efforts can cast light on prevalent yet overlooked metabolites in the microbiome.

Bacterial cysteate dissimilatory pathway involves a racemase and d-cysteate sulfo-lyase.

The sulfite-reducing bacterium Bilophila wadsworthia, a common human intestinal pathobiont, is unique in its ability to metabolize a wide variety of sulfonates to generate sulfite as a terminal electron acceptor (TEA). The resulting formation of H2S is implicated in inflammation and colon cancer. l-cysteate, an oxidation product of l-cysteine, is among the sulfonates metabolized by B. wadsworthia, although the enzymes involved remain unknown. Here we report a pathway for l-cysteate dissimilation in B. wadsworthia RZATAU, involving isomerization of l-cysteate to d-cysteate by a cysteate racemase (BwCuyB), followed by cleavage into pyruvate, ammonia and sulfite by a d-cysteate sulfo-lyase (BwCuyA). The strong selectivity of BwCuyA for d-cysteate over l-cysteate was rationalized by protein structural modeling. A homolog of BwCuyA in the marine bacterium Silicibacter pomeroyi (SpCuyA) was previously reported to be a l-cysteate sulfo-lyase, but our experiments confirm that SpCuyA too displays a strong selectivity for d-cysteate. Growth of B. wadsworthia with cysteate as the electron acceptor is accompanied by production of H2S and induction of BwCuyA. Close homologs of BwCuyA and BwCuyB are present in diverse bacteria, including many sulfate- and sulfite-reducing bacteria, suggesting their involvement in cysteate degradation in different biological environments.

Has the digital economy improved income inequality for ethnic minorities? The case of China.

This paper examines how China's ethnic minorities' income equality has changed due to the digital economy's development. The study focuses on the critical analysis of the legal system by juridical analysis combined with doctrinal and textual analysis. Furthermore, the article makes the argument convictive by developing econometric models and heterogeneity analysis. Through a dialectical discussion, this paper shows a shared understanding of what the term "digital economy" means in Chinese society, and that income equality for ethnic minorities in the digital economy has both positive and negative effects. On the one hand, the digital economy is conducive to raising income levels and reducing the income gap between Han Chinese and ethnic minorities; however, on the other hand, the digital economy exacerbates the income gap between Han Chinese and ethnic minorities among low-income groups. As a result, disputes over income equality for ethnic minorities in the digital economy are more pronounced among low-income groups. The institutional causes of these problems include the inadequacy of China's digital economy policies for ethnic minorities and the shortcomings of China's legal system for labor protection. The Chinese government should renew the Chinese Constitution, labor law, and employment protection policies to improve the present situation. Based on China's experience, other countries should have pragmatic attitudes to revise the laws and regulations and explore some target measures, such as the digital services tax, to help ethnic minorities.

Lanthipeptides from the Same Core Sequence: Characterization of a Class II Lanthipeptide Synthetase from Microcystis aeruginosa NIES-88.

Class II lanthipeptide synthetases (LanMs) are relatively promiscuous to core peptide variations. Previous studies have shown that different LanMs catalyze identical reactions on the same core sequence fused to their respective cognate leaders. We characterized a new LanM enzyme from Microcystis aeruginosa NIES-88, MalM, and demonstrated that MalM and ProcM exhibited disparate dehydration and cyclization patterns on identical core peptides. Our study provided new insights into the regioselectivity of LanMs and showcased an appropriate strategy for lanthipeptide structural diversity engineering.

Cytochalasins from Xylaria sp. CFL5, an Endophytic Fungus of Cephalotaxus fortunei.

Three previously undescribed cytochalasins, named xylariasins A‒C (1‒3), together with six known ones (4‒9) were isolated from Xylaria sp. CFL5, an endophytic fungus of Cephalotaxus fortunei. The chemical structures of all new compounds were elucidated on the basis of extensive spectroscopic data analyses and electronic circular dichroism calculation, as well as optical rotation calculation. Biological activities of compounds 1, 4‒9 were evaluated, including cytotoxic, LAG3/MHC II binding inhibition and LAG3/FGL1 binding inhibition activities. Compounds 6 and 9 possessed cytotoxicity against AGS cells at 5 µM, with inhibition rates of 94% and 64%, respectively. In addition, all tested isolates, except compound 6, exhibited obvious inhibitory activity against the interaction of both LAG3/MHC II and LAG3/FGL1. Compounds 1, 5, 7, and 8 inhibited LAG3/MHC II with IC50 values ranging from 2.37 to 4.74 µM. Meanwhile, the IC50 values of compounds 1, 7, and 8 against LAG3/FGL1 were 11.78, 4.39, and 7.45 µM, respectively.

Halimane and labdane diterpenoids from Leonurus japonicus and their anti-inflammatory activity.

Ten highly oxygenated diterpenoids (nine undescribed ones) were isolated from the aerial parts of Leonurus japonicus Houtt. 14,15-Dinor-labd-5,8-dien-3,13-dione was a 14,15-dinor-labdane diterpenoid possessing a C18 skeleton. 7ß,9α-Dihydroxy-6-oxo-labd-13-en-15,16-amide represented a rare example of labdane diterpenoid featuring an α,ß-unsaturated-γ-lactam moiety. The structures of all compounds were elucidated using spectroscopic data analyses and comparisons. The effects of these obtained compounds on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 cells were evaluated.(10R*,13R*,15R*)-15,16-Epoxy-6,13-dihydroxy-15-methoxy-labda-5,8-dien-7-one inhibited NO production with an IC50 value of 40.1 µM.

Phytotoxic neo-clerodane diterpenoids from the aerial parts of Scutellaria barbata.

Bioactivity guided the isolation of extracts from the aerial parts Scutellaria barbata D. Don to discover neo-clerodane diterpenoids with potent phytotoxic activity. Of the 34 isolates, 13 neo-clerodane diterpenoids were described for the first time. The structures of these undescribed compounds were elucidated by extensive analysis of NMR spectroscopic data, and the absolute configurations of scutebarbolides A and L and scutebata W were determined by X-ray diffraction. The phytotoxic activity of all compounds against the growth of the roots and shoots of L. perenne and L. sativa seedlings were first reported, and some compounds showed considerable inhibitory effects, especially scutebarbolide K, whose inhibition rates were higher than those of the positive control at concentrations ranging from 25 to 200 µg/mL. When L. perenne and L. sativa seedlings were treated at a concentration of 200 µg/mL, scutebarbolide K caused wilting symptoms on and finally death of these two tested plant seedlings. In addition, the structure-activity relationships of these neo-clerodane diterpenoids were also discussed.

Anti-inflammatory evaluation and structure-activity relationships of diterpenoids isolated from Euphorbia hylonoma.

A phytochemical investigation to obtain chemical components with potential anti-inflammatory activity from E. hylonoma led to the isolation of nine new ent-isopimarane diterpenoids (1 and 3-10), a new ent-rosane diterpenoid (11), along with eight known ones (2 and 12-18) using various chromatographic techniques. Compounds 3, 4, 5, and 10 were rare examples of the epoxy-ent-isopimarane. The structures of these new compounds were confirmed by extensive spectroscopic data, crystal X-ray diffraction analysis, and electronic circular dichroism. And the isolates were evaluated for their inhibitory effects on nitric oxide production induced by lipopolysaccharide in RAW 264.7 cells. The results showed that compounds 2 and 12 exhibited noteworthy inhibitory effects against NO production with IC50 values of 7.12 and 12.73 µM, respectively, which were better than positive control (IC50 = 41.41 µM). The possible mechanism that compounds 2 and 12 could inhibit NO production was investigated by the Western blotting experiments.

Labdane-Type Diterpenoids from Leonurus japonicus and Their Plant-Growth Regulatory Activity.

Thirteen new labdane-type diterpenoids 1-6, 9-11, 13, 14, 18, and 19 and seven known ones were isolated from the aerial parts of Leonurus japonicus. Compounds 1-5 represent rare examples of labdane-type diterpenoids, of which compounds 1-4 carry an N-chain linked at C-7 in their B-ring and compound 5 featured an α,ß-unsaturated-γ-lactam moiety. The structures and absolute configurations of these new diterpenoids were characterized by a combination of spectroscopic techniques, X-ray crystallography, electronic circular dichroism, and calculated specific rotations. The plant-growth regulatory activity of these compounds on the growth of the roots and shoots of Lactuca sativa and Lolium perenne seedlings were evaluated. Compound 3 showed a broad-spectrum inhibitory activity with the inhibition rates ranging from 60 to 83.5% at a concentration of 200 µg/mL, which were as active as those of glyphosate. Compound 8 had a selective inhibitory activity against the growth of the roots of L. perenne seedlings with an inhibition rate of 81.7%. However, compounds 11 and 16 exhibited significant stimulation effects on the roots of L. sativa with stimulation rates of 59.8 and 65.3%, respectively. In addition, compounds 3 and 8 exhibited inhibitory effects on the germination of L. perenne seeds.

Highly Oxygenated Triterpenoids and Rare Tetraterpenoids from Abies chensiensis and Their Antibacterial Activity.

Nine new cycloartane triterpenoids (1, 2, 4, 7, 8, 12, 15, 17, and 18) and two new rare tetraterpenoids (24 and 25) formed via a [4 + 2] Diels-Alder cycloaddition between a lanostane triterpenoid and a monoterpenoid, along with 14 previously known triterpenoids, were isolated from the bark of the branches of Abies chensiensis. The structures and absolute configurations of new compounds were elucidated based on spectroscopic data, X-ray diffraction analysis, and electronic circular dichroism. Some of the isolates were evaluated for their antibacterial activity by determining their minimum inhibitory concentrations and growth inhibition curves and examining for morphological alterations. Among the compounds tested, the new cycloartane triterpenoid 8 was the most active against Bacillus subtilis. Thus, morphological alterations of B. subtilis on treatment with 8 were observed by scanning electron microscopy, showing that the cells were irregular, wrinkled, and disrupted.

Phytotoxic Diterpenoids from Plants and Microorganisms.

Phytotoxic natural products with either unique or various structures are one of the most abundant sources for the discovery of potential allelochemicals, natural herbicides, and plant growth regulators. Phytotoxic diterpenoids, a relatively large class of natural products, play an important role in the plant-plant or plant-microorganism interactions. This article argues that the phytotoxic diterpenoids isolated from the plants and microorganisms can either inhibit the seed germination and the growth of plant seedlings or lead to some disease symptoms on the tested plant tissues and plant seedlings.