High intestinal isoleucine is a potential risk factor for food allergy by regulating the mTOR/AKT pathway in dendritic cells.

Food allergy is a global food safety problem with a growing prevalence. People in industrial regions are more susceptible to allergy, but the mechanisms behind this are not fully understood. In this study, the probiotic Lactobacillus casei Zhang (LcZ) was administered to allergic individuals and the impact on allergy-related factors were determined. LcZ alleviated allergenic responses, and there was a significant correlation between the intestinal isoleucine content and IgE concentration. Metagenomics results suggest that the metabolism of the gut microbiota is a source of isoleucine. In a mouse model of food allergy, a high isoleucine diet exacerbated allergic responses and increased the activity of allergenic dendritic cell. In a dendritic cell model, a protein array revealed that the mTOR/AKT pathway mediated the function of isoleucine, and molecular docking suggested that Sestrin2 could be the potential receptor. Overall, this study revealed the role of isoleucine in promoting food allergy, elucidated the underlying mechanisms, and suggested that a high intake of isoleucine could be a potential risk factor for food allergy.

Synthesis of 11-aminoalkoxy substituted benzophenanthridine derivatives as tyrosyl-DNA phosphodiesterase 1 inhibitors and their anticancer activity.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme that repairs DNA lesions caused by the trapping of DNA topoisomerase IB (TOP1)-DNA break-associated crosslinks. TDP1 inhibitors have synergistic effect with TOP1 inhibitors in cancer cells and can overcome cancer cell resistance to TOP1 inhibitors. Here, we report the synthesis of 11-aminoalkoxy substituted benzophenanthridine derivatives as selective TDP1 inhibitors and show that six compounds 14, 16, 18, 20, 25 and 27 exhibit high TDP1 inhibition potency. The most potent TDP1 inhibitor 14 (IC50 = 1.7 ±â€¯0.24 µM) induces cellular TDP1cc formation and shows synergistic effect with topotecan in four human cancer cell lines MCF-7, A549, H460 and HepG2.

Pyranodipyran Derivatives with Tyrosyl DNA Phosphodiesterase 1 Inhibitory Activities and Fluorescent Properties from Aspergillus sp. EGF 15-0-3.

Four new benzodipyran racemates, namely (±)-aspergiletals A-D (3-6), representing a rare pyrano[4,3-h]chromene scaffold were isolated together with eurotiumide G (1) and eurotiumide F (2) from the soft-coral-derived fungus Aspergillus sp. EGF 15-0-3. All the corresponding optically pure enantiomers were successfully separated by a chiral HPLC column. The structures and configurations of all the compounds were elucidated based on the combination of NMR and HRESIMS data, chiral separation, single-crystal X-ray diffraction, quantum chemical 13C NMR, and electronic circular dichroism calculations. Meanwhile, the structure of eurotiumide G was also revised. The TDP1 inhibitor activities and photophysical properties of the obtained compounds were evaluated. In the TDP1 inhibition assay, as a result of synergy between (+)-6 and (-)-6, (±)-6 displayed strong inhibitory activity to TDP1 with IC50 values of 6.50 ± 0.73 µM. All compounds had a large Stokes shift and could be utilized for elucidating the mode of bioactivities by fluorescence imaging.

Wide-field parallel mapping of local spectral and topographic information with white light interference microscopy.

Fourier analysis of interferograms captured in white light interference microscopy is proposed for performing simultaneous local spectral and topographic measurements at high spatial resolution over a large field of view. The technique provides a wealth of key information on local sample properties. We describe the processing and calibration steps involved to produce reflectivity maps of spatially extended samples. This enables precise and fast identification between different materials at a local scale of 1 µm. We also show that the recovered spectral information can be further used for improving topography measurements, particularly in the case of samples combining dielectric and conducting materials in which the complex refractive index can result in nanometric height errors.

Thuricin†Z: A Narrow-Spectrum Sactibiotic that Targets the Cell Membrane.

Sactionine-containing antibiotics (sactibiotics) are a growing class of peptide antibiotics belonging to the ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily. We report the characterization of thuricin Z, a novel sactibiotic from Bacillus thuringiensis. Unusually, the biosynthesis of thuricin Z involves two radical S-adenosylmethionine (SAM) enzymes, ThzC and ThzD. Although ThzC and ThzD are highly divergent from each other, these two enzymes produced the same sactionine ring in the precursor peptide ThzA in vitro. Thuricin Z exhibits narrow-spectrum antibacterial activity against Bacillus cereus. A series of analyses, including confocal laser scanning microscopy, ultrathin-sectioning transmission electron microscopy, scanning electron microscopy, and large-unilamellar-vesicle-based fluorescence analysis, suggested that thuricin Z binds to the bacterial cell membrane and leads to membrane permeabilization.

Effects of microwave heating of wheat on its functional properties and accelerated storage.

The effect of microwave heating wheat grains (700 W for 0-60 s) on gluten, farinograph, pasting properties and baking (steamed bread and biscuit) of flour was studied. The lipase (LA) and lipoxygenase (LOX) activities of the microwave-treated wheat were monitored, and the accelerated storage at 35 °C of whole wheat flour was also investigated. The results showed that the gluten, farinograph properties and viscosity were influenced to a small extent when microwave treatment time was less than or equal to 20 s and the temperature of the grains was less than or equal to 56 °C. Texture profile analysis indicated that steamed bread made from wheat treated by microwave for 20 s was softer and of better quality. Microwave treatment for longer periods (≥30 s) increased the temperature ≥68 °C, that damaged the gluten and made wheat unsuitable for making steamed bread; however, suitable for making food with lower gluten requirements, such as biscuits. The results obtained from enzyme activity and accelerated storage experiments demonstrated that microwave treatment could inactivate LA and LOX and extend the shelf-life.

[Karyotype analysis and fluorescence in situ hybridization detection of 122 patients with myelodysplastic syndrome].

OBJECTIVE: To assess the value of karyotype analysis and fluorescence in situ hybridization(FISH) assay for the diagnosis of myelodysplastic syndrome (MDS). METHODS: The karyotypes of 122 initially treated MDS patients were analyzed with conventional R-banding and FISH using probes including GLP CSF1R/D5S23, D5S721, GLP EGR1/D5S23, D5S721, GLP D7S486/CSP7, GLP D7S522/CSP7, GLP D20S108, CSP8 and CSP X/Y. RESULTS: The detection rate of chromosomal abnormalities was 54.9% for the 122 patients. Among these, those involving 3 or more chromosomes are most common (16.4%), followed by +8(14.8%), -7/7q-(7.4%), -5/5q-(5.7%), 20q-(2.5%), and -Y in male patients (5.0%). Two MDS-RAEB II patients detected with t(8;21) should be diagnosed with acute myelocytic leukemia. FISH analysis showed that 54 patients were positive (44.3%). Among these, 30.3% had CSP8 amplification, followed by GLP D7S486/CSP7 and GLP D7S522/CSP7 deletion (12.3%), GLP CSF1R/D5S23, D5S721 and GLP EGR1/D5S23, D5S721 deletion (9.8%), GLP D20S108 deletion (7.4%), and CSPX/Y deletion (5%). CONCLUSION: With a detection rate of 54.9%, R-banding still constitutes the basic examination for MDS. As detection of interstitial chromosomal abnormalities in MDS can be greatly enhanced by FISH, combined karyotype analysis and FISH can improve the diagnosis of MDS and facilitate assessment of its prognosis.

The cytokines (IFN-gamma, IL-2, IL-4, IL-10, IL-17) and Treg cytokine (TGF-beta1) levels in adults with immune thrombocytopenia.

Previous studies have indicated that autoimmune diseases might be caused by an imbalance of T helper cells (Th), cytokines, and regulatory T cells (Treg) cytokines. We measured the plasma concentrations of Th1-associated cytokines (IFN-gamma, IL-2), Th2 -associated cytokines (IL-4, IL-10), Th17-associated cytokine (IL-17) and Treg -associated cytokine (TGF-beta1) in adult patients with immune thrombocytopenia (ITP) and evaluated their clinical relevance. Plasma IFN-gamma, IL-2, IL-4, IL-10, IL-17 and TGF-beta1 concentrations of 52 ITP patients and 30 age- and sex-matched healthy controls were measured by enzyme-linked immunosorbent assay method (ELISA). Concentration of Th2 cytokines (IL-4 and IL-10) were significantly higher in ITP patients compared to controls (P < 0.05). However, concentrations of Th1 cytokines (IFN-gamma, IL-2), Th17 cytokine (IL-17) and Treg cytokine (TGF-beta1) were lower in ITP patients (P < 0.05). Concentration of IL-17 was significantly higher in chronic ITP patients compared to severe ITP patients (P < 0.05), and no significant difference of cytokine concentration among the other subgroups in ITP patients was found. Among the ITP patients, concentration of IFN-gamma correlated positively and significantly with PAIgG (r = 0.48, P = 0.02). A significant correlation was neither found between other cytokine levels and platelet count, nor between cytokine levels and megakaryocytes number, nor between cytokines levels and PAIgG or GPIIb/IIIa and/or GPIb/IX autoantibodies. The present study demonstrates that an imbalance of Th and Treg cytokines may mediate the pathogenesis of ITP.

Regional background ozone estimation for China through data fusion of observation and simulation.

Regional background ozone (O3_RBG) is an important component of surface ozone (O3). However, due to the uncertainties in commonly used Chemical Transport Models (CTMs) and statistical models, accurately assessing O3_RBG in China is challenging. In this study, we calculated the O3_RBG concentrations with the CTM - Brute Force Method (BFM) and constrained the results with site observations of O3 with the multiple linear regression (MLR) model. The annual average O3_RBG concentration in China region in 2020 is 35 ± 4 ppb, accounting for 81 ± 5 % of the maximum 8-h average O3 (MDA8 O3). We applied the random forest and Shapley additive explanations based on meteorological standardization techniques to separate the contributions of meteorology and natural emissions to O3_RBG. Natural emissions contribute more significantly to O3_RBG than meteorology in various Chineses regions (30-40 ppb), with higher contributions during the warm season. Meteorological factors show higher contributions in the spring and summer seasons (2-3 ppb) than the other seasons. Temperature and humidity are the primary contributors to O3_RBG in regions with severe O3 pollution in China, with their individual impacts ranging from 30 % to 62 % of the total impacts of all meteorological factors in different seasons. For policy implications, we tracked the contributions of O3_RBG and local photochemical reaction contributions (O3_LC) to total O3 concentration at different O3 levels. We found that O3_LC contribute over 45 % to MDA8 O3 on polluted days, supporting the current Chinese policy of reducing O3 peak concentrations by cutting down precursor emissions. However, as the contribution of O3_RBG is not considered in the policy, additional efforts are needed to achieve the control groal of O3 concentration. As the implementation of stringent O3 control measurements in China, the contribution of O3_RBG become increasingly significant, suggesting the need for attention to O3_RBG and regional joint prevention and control.

Synthesis and Biological Activities of 11- and 12-Substituted Benzophenanthridinone Derivatives as DNA Topoisomerase IB and Tyrosyl-DNA Phosphodiesterase 1 Inhibitors.

Herein, a series of 11- or 12-substituted benzophenanthridinone derivatives was designed and synthesized for the discovery of dual topoisomerase IB (TOP1) and tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors. Enzyme-based assays indicated that two compounds 12 and 38 showed high TOP1 inhibitory potency (+++), and four compounds 35, 37, 39 and 43 showed good TDP1 inhibition with IC50 values ranging from 10 to 18 µM. 38 could induce cellular TOP1cc formation, resulting in the highest cytotoxicity against HCT-116 cells (0.25 µM). The most potent TDP1 inhibitor 43 (10 µM) could induce cellular TDP1cc formation and enhance topotecan-induced DNA damage and showed strong synergistic cytotoxicity with topotecan in both MCF-7 and MCF-7/TDP1 cells.

[Cadmium Enrichment and Bioavailability of Quaternary Profiles in Nansha District, Guangzhou, China].

Comprehending the distribution pattern and enrichment rule of the heavy metal cadmium (Cd) in soil and grasping its activity and influencing factors is crucial for guaranteeing the soil environment safety of agricultural and construction land and improving the overall quality of the soil environment. The concentration of heavy metal Cd in the quaternary profile of Nansha was measured, and the pollution level was evaluated using the geographical accumulation index (Igeo) and potential ecological risk index (Er). Then, we determined the correlation between the total amount of Cd and the physicochemical properties of the soil using factor analysis (FA-MLR). The results showed that the average content of Cd in shallow soil (0-20 cm) in the Nansha area was 0.54 mg·kg-1, and the soil was mainly weakly acidic and neutral. The average content of Cd in deep soil (150-200 cm) was 0.42 mg·kg-1, and the soil was mainly neutral. At the same time, the variation coefficient of Cd content in shallow soil was significantly greater than that in deep soil, and Cd content tended to be consistent with the increase in depth. The Cd content of quaternary sediments showed a bimodal distribution with depth, reaching a peak at 20-25 m and 5-10 m, respectively, whereas the core sediments in this section were mostly marine sediments of silt and silty clay, with high cation exchange capacity and organic matter. The Igeo and Er of Cd in the fine-grained sediments dominated by clayey soil were significantly higher than those in the coarse-grained sediments dominated by sandy soil. The difference in soil pH value led to the different trend of Cd content with depth; the migration amount and vertical migration depth of Cd in deep soil were greater in the acidic environment. The influence of pH change on the migration and transformation of Cd was not completely reflected in the influence on the total amount of Cd, but more importantly, it changed the effective state of Cd, thus affecting the bioavailability of Cd. The unstable Cd composed of water-soluble, ion-exchangeable, and carbonate states accounted for 37.92%-49.10% of the total Cd, resulting in a strong instability of soil Cd. Further investigation on the migration and toxicity of heavy metals associated with human health risks is needed in future studies.

Adsorption and pH Values Determine the Distribution of Cadmium in Terrestrial and Marine Soils in the Nansha Area, Pearl River Delta.

Cadmium is a toxic element with a half-life of several decades, which can accumulate in the human body by entering the food chain and seriously harm health. The cadmium adsorption and desorption processes in the soil directly affect the migration, transformation, bioavailability, and ecotoxicity of this element in soil-plant systems. Coastal zones are located in the transitional zone between land and sea, and large amounts of terrigenous material input have important environmental effects on this ecosystem. The pH, hydrodynamic conditions, soil organic matter (SOM), and other factors defining the sea-land interaction within the sedimentary environment are significantly different from those defining land facies. In order to study the key factors affecting cadmium adsorption in soils at the sea-land interface in the Nansha area of the Pearl River Delta, a test was conducted on a column of undisturbed soil. The results showed that the adsorption constant KF and the Cd2+ adsorption capacity of marine soils were higher than those of terrestrial soils. However, the saturation adsorption of cadmium in terrestrial sediments was higher than in marine sediments. Soil pH was an important factor affecting cadmium adsorption capacity in both terrestrial and ma-rine sediments. Neutral and alkaline topsoil conditions inhibited the vertical migration of cadmium, while the acidic environment favored it. The higher the clay and SOM were, the stronger the Cd2+ adsorption capacity of the soil was. These findings suggest that the distribution of cadmium in marine and continental sedimentary soils is not only related to adsorption, but also to the physical and chemical processes occurring in different sedimentary environments.

Discovery, enantioselective synthesis of myrtucommulone E analogues as tyrosyl-DNA phosphodiesterase 2 inhibitors and their biological activities.

As a recently discovered DNA repair enzyme, tyrosyl-DNA phosphodiesterase 2 (TDP2) can specifically repair topoisomerase 2 (TOP2)-mediated DNA damage, resulting in cancer cell resistance to TOP2 inhibitors. Its inhibitors can enhance the anticancer efficacy of TOP2 inhibitors. In this work, we report the discovery of natural product myrtucommulone E as selective TDP2 inhibitor and its first enantioselective total synthesis through a pivotal CPA-catalyzed Michael addition reaction. A series of myrtucommulone E analogues were asymmetrically synthesized and evaluated for TDP2 and TDP1 inhibitions, and cytotoxicity. Analogue (+)-29 shows good TDP2 inhibition potency (5.4 ± 0.25 µM), but no TDP1 inhibition at 100 µM concentration, and can significantly enhance the cytotoxicity of TOP2 inhibitor etoposide in both DU145 (CI = 0.26) and DT40 hTDP2 cells (CI = 0.48).

Intestinal proline is a potential anti-allergy factor for allergy diagnosis and therapy.

Allergy has become a public health problem worldwide, but effective diagnostic and therapeutic approaches are limited currently. Amino acids are essential macronutrients that potentially participated in the allergy process. This work aimed to investigate whether amino acids can be applied as a mediator for allergy diagnosis and therapy. Two cohort studies were performed to investigate the correlation between fecal amino acids and allergy responses, and a spleen cell model was used to validate the role of amino acids in regulating allergy. In a cohort study with 193 volunteers, fecal proline was found to be negatively correlated with serum IgE, and detailed data analysis revealed that people with high-IgE-mediated allergy had decreased odds of high intestinal proline. In another cohort study with distinct allergic and non-allergic individuals, proline concentration was significantly lower in the allergic group. Daily diet and metagenomics analysis showed that the proline intake and microbiota amino acid metabolism were not significantly different, implying that the body's proline metabolism might be different between allergic and non-allergic individuals. Furthermore, the spleen cell model demonstrated that proline specifically targeted Th2 and Treg activity. Overall, this work revealed a tight correlation between gut proline and serum IgE, indicating proline as a promising biomarker and a potential therapeutic method for allergic diseases.

[Bioavailability and Ecological Risk Assessment of Cadmium in the Sea-Land Interaction Sediments of the Pearl River Delta].

Cadmium (Cd) pollution poses a threat to human health, and research on Cd bioavailability as well as its ecological risk assessment can help prevent and mitigate Cd hazards. The enrichment characteristics and variability of Cd were investigated in sea-land interaction soil fractions and the associated environmental and ecological risks were evaluated using the accumulation index (Igeo), potential ecological hazard index (Er), and risk assessment coding (RAC). The results showed that:① The Cd content of miscellaneous fill material was typically lower than 0.3 mg·kg-1 and that of plain full was higher than 0.3 mg·kg-1. The Cd content of marine sediment was significantly higher than that of continental sediments, averaging 0.36 and 0.10 mg·kg-1, respectively. The concentration of Cd in marine sediments buried at shallow depths (<5 m) was generally higher than at greater depths (>5 m). ② There was a moderate correlation between Cd and CEC in artificial fill (Q4ml; correlation coefficient=0.52, P<0.05). There was a weak correlation between Cd and organic matter in the marine sediments (correlation coefficient=0.49, P<0.05). Total cadmium and the physical and chemical properties of soil had a significant influence on the fraction of soil cadmium. ③ The Igeo of artificially fill and marine sediment was dominated by the relationship 1 < Igeo < 2, which indicated a moderate level of pollution. The Er of artificial fill and marine sediment was mainly 80 < Er < 160, indicating a high potential ecological hazard. Soil acid-extractable Cd accounted for more than 50% of the total Cd in each drill hole, which generally indicated a very high potential ecological risk. These results provide a basis for environmental and agricultural decision-making and provide theoretical guidance for soil pollution investigations and remediation.

Long-term exposure to low doses of bisphenol S has hypoglycaemic effect in adult male mice by promoting insulin sensitivity and repressing gluconeogenesis.

Bisphenol S (BPS), an industrial chemical that is a structural analogue of bisphenol A, has been widely reported to be involved in various biological processes. Epidemiological studies have demonstrated that exposure to BPS is associated with dysglycaemia-related health outcomes. The role of BPS in glucose metabolism, however, remains controversial. In this study, we aimed to investigate the effects of chronic exposure to environmentally relevant concentrations of BPS on glucose metabolism in different nutritionally conditioned mice. Our results revealed that 1-month exposure to a BPS dosage of 100 µg/kg bw slightly increased the insulin sensitivity of normal diet-fed mice, and that this effect was enhanced after 3-month exposure. It was also found that BPS exposure attenuated insulin resistance and reduced gluconeogenesis in high-fat diet-fed mice. Consequently, the concentrations of hepatic metabolites related to glucose metabolism were altered in both groups of mice. Moreover, thyroid hormone signalling was disrupted after BPS administration in both groups of mice. Taken together, our results demonstrated that chronic exposure to environmentally relevant concentrations of BPS exerted an unexpected hypoglycaemic effect in mice of different nutritional statuses, and that this was partly attributable to disrupted thyroid hormone signalling.

[Application of fluorescence in situ hybridization technique in diagnosis of variant Ph chromosome translocation and Ph-negative chronic myelocytic leukemia].

OBJECTIVE: To explore the value of fluorescence in situ hybridization (FISH) technique in diagnosis of variant Ph chromosome translocation (VT) and Ph chromosome-negative chronic myelocytic leukemia (CML). METHODS: Nine CML patients with VT and 2 Ph chromosome-negative CML patients confirmed by R banding were assayed with dual color-dual fusion BCR/ABL probe by FISH. RESULTS: The 9 patients with VT involved chromosomes 1, 3, 5, 12, 13, 15, 17 and 21 besides chromosomes 9 and 22, and some of them showed recurrent aberrations; FISH results were positive and the signal feature was 2R2G1Y. The 2 Ph-negative CML patients had normal karyotypes; FISH was positive and the signal feature was 1R1G2Y and 1R1G1Y respectively. CONCLUSION: FISH can provide better diagnosis for CML with VT and Ph-negative CML. Abnormal karyotype and marker gene changes can be assessed based on the signal feature of the positive cell. So FISH is a complementary method to banding technique in diagnosis of CML.

[Content and Distribution of Cadmium in Soil and Fluvial Sediments in the Sea-Land Interaction Zone].

Cadmium pollution poses a threat to human health. The examination of spatial distribution of Cd in soils can be used to assess the risks posed to humans and the environment. The enrichment characteristics and variation rules of heavy metal cadmium in the soil were revealed by analyzing the concentration and fractions of Cd in the soil at different depths in the sea-land interaction zone. The results showed that: ① the concentration of Cd in the surface water of Nansha was lower than 0.0001 mg ·L-1, and the physical and chemical properties of river sediments showed spatial differences with the boundary of "Shang Heng-li River". Cd was mainly deposited in the north of the "Shang Heng-li River", with the mean total Cd of 2.71 mg ·kg-1. The total Cd in the sediment of the "Shang Heng-li River" and the rivers south of it were 0.062-0.39 mg ·kg-1, which caused minimal harm to the marine environment. ② The content of Cd in the soil profile gradually decreased with an increase in soil burial depth. The median content of Cd in the five layers, including 0-20 cm, 20-50 cm, 50-90 cm, 90-140 cm, and 140-200 cm, were 0.51, 0.50, 0.45, 0.42, and 0.33 mg ·kg-1, respectively, and the dispersion degree gradually decreased with an increase in buried depth; the vertical migration amount and migration depth of Cd increased significantly in soils with pH less than 5. ③ The residual Cd in the soil accounted for approximately 40%, and the trend was typically flat with a change in buried depth. The median proportion of acid soluble Cd was consistent with the change in pH and increased with an increase in the buried depth of the profile, while the median proportion of reducible Cd was consistent with the change in iron and manganese content, and decreased with an increase in buried depth of section. These results have important guiding significance for the regional prevention and control of Cd pollution in farmland surrounding cities and the treatment and remediation of polluted soil.

Distribution, Ecological Risk Assessment, and Bioavailability of Cadmium in Soil from Nansha, Pearl River Delta, China.

Background: Cadmium (Cd) pollution poses a threat to human health. Examination of the spatial distribution of Cd in soils can be used to assess the risks posed to humans and the environment. Objective: This study determined the enrichment rules and factors influencing Cd pollution in Nansha, and evaluated the pollution characteristics and bioavailability of Cd in quaternary sediments through 7 deep soil profiles (0-200 cm), 4 boreholes, and 348 topsoil (0-20 cm) samples. Methods: The geo-accumulation index (Igeo) and the potential ecological risk index (Er) were used to assess ecological risk, and bioavailability was determined using multivariate, spatial distribution, and correlation matrix analyses. Results: From the Er, 52% of Nansha was classed as being at very high risk of Cd pollution; a further 36% was classed as dangerous. Cadmium was more abundant in clay soils than in sandy soils. Bioavailable Cd in quaternary sediments was significantly affected by the total Cd, and labile Cd accounted for more than half of the total Cd. Changes in pH mainly affected bioavailable Cd rather than total Cd, affecting the overall bioavailability of Cd. Conclusions: Nansha soils are commonly and seriously contaminated with Cd. An appropriate remediation treatment approach should be used to reduce Cd bioavailability. Furthermore, planting structures in farmland should be adjusted to avoid the impact of heavy metals on human health.

Convergent evolution of the Cys decarboxylases involved in aminovinyl-cysteine (AviCys) biosynthesis.

S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) is a unique motif found in several classes of ribosomally synthesized and post-translationally modified peptides (RiPPs). Biosynthesis of AviCys requires flavin-dependent Cys decarboxylases, which are highly divergent among different RiPP classes. In this study, we solved the crystal structure of the cypemycin decarboxylase CypD. We show that CypD is structurally highly similar to lanthipeptide decarboxylases despite the absence of sequence similarities between them. We further show that Cys decarboxylases from four RiPP classes have evolved independently and form two major clusters. These results reveal the convergent evolution of AviCys biosynthesis and suggest that all the flavin-dependent Cys decarboxylases likely have a similar Rossmann fold despite their sequence divergences.