The role of cilia during organogenesis in zebrafish.

Cilia are hair-like organelles that protrude from the surface of eukaryotic cells and are present on the surface of nearly all human cells. Cilia play a crucial role in signal transduction, organ development and tissue homeostasis. Abnormalities in the structure and function of cilia can lead to a group of human diseases known as ciliopathies. Currently, zebrafish serves as an ideal model for studying ciliary function and ciliopathies due to its relatively conserved structure and function of cilia compared to humans. In this review, we will summarize the different types of cilia that present in embryonic and adult zebrafish, and provide an overview of the advantages of using zebrafish as a vertebrate model for cilia research. We will specifically focus on the roles of cilia during zebrafish organogenesis based on recent studies. Additionally, we will highlight future prospects for ciliary research in zebrafish.

Herbal compound cepharanthine attenuates inflammatory arthritis by blocking macrophage M1 polarization.

OBJECTIVE: Cepharanthine (CEP) is a drug candidate for tumor, viral infection, and some inflammatory diseases, but its effect on rheumatoid arthritis (RA) and the underlying mechanism are incompletely understood. METHODS: CEP was administered intraperitoneally to a collagen-induced arthritis (CIA) model. Joints went radiological and histological examination and serum cytokines were examined with cytometry-based analysis. M1 macrophages were induced from THP-1 cells or mouse bone marrow-derived macrophages with LPS and IFN-γ. Bulk RNA-seq was performed on macrophage undergoing M1-polarizatioin. Western blotting was applied to determine pathways involved in monocyte chemotaxis and polarization. Glycolysis metabolites were measured by chemiluminescence while glycolytic enzymes were examined by quantitative PCR. RESULTS: We found CEP significantly ameliorated synovial inflammation and joint destruction of CIA mice. It downregulated TNF-α levels in serum and in joints. The number of M1 macrophages were reduced in CEP-treated mice. In vitro, CEP inhibited monocyte chemotaxis to MCP-1 by downregulating CCR2 and reducing ERK1/2 signaling. Additionally, CEP suppressed M1 polarization of macrophages induced by LPS and IFN-γ. Genes involved in IFN-γ signaling, IL-6-JAK/STAT3 signaling, glycolysis, and oxidative phosphorylation process were downregulated by CEP. Several enzymes critically involved in glycolytic metabolism were suppressed by CEP, which resulted in reduced citrate in M1-polarizing macrophages. The inhibitory effect of CEP on macrophage polarization might be attributed to the blockage of TLRs-MyD88/IRAK4-IRF5 signaling pathway together with suppression of overactivated glycolytic metabolism in M1-polarizing macrophages. CONCLUSION: CEP attenuated joint inflammation by suppressing monocyte chemotaxis and proinflammatory differentiation. It has the potential to be developed into a complementary or alternative therapy for RA.

The varied roles of pilA-N, omcE, omcS, omcT, and omcZ in extracellular electron transfer by Geobacter sulfurreducens.

Geobacter sulfurreducens mediates extracellular electron transfer (EET) reactions with different substrates, such as solid-phase Fe(III)-containing minerals, anodes and the cells of Geobacter metallireducens. To compare their roles in EET, the pilA-N, omcE, omcS, omcT and omcZ genes of G. sulfurreducens were systematically deleted. All mutants showed impaired and varied ability to form biofilms on nonconductive surface. Deletion of omcE also impaired bacterial ability to reduce ferrihydrite, but its impacts on the ability for anode reduction and the co-culture of G. metallireducens-G. sulfurreducens were minimal. The mutant without omcS showed diminished ability to reduce ferrihydrite and to form the co-culture, but was able to regain its ability to reduce anodes. Deletion of omcT, omcZ or pilA-N alone impaired bacterial ability to reduce ferrihydrite and anodes and to form the co-culture. Deletion of all tested genes abolished bacterial ability to reduce ferrihydrite and anodes. Triple-deletion of all omcS, omcT and omcZ abolished the ability of G. sulfurreducens to co-culture with G. metallireducens. However, deletion of only omcZ or pilA-N or both omcS and omcT abolished the ability of G. sulfurreducens without hydrogenase gene hybL to co-culture with G. metallireducens, which show their indispensable roles in direct electron transfer from G. metallireducens to G. sulfurreducens. Thus, the roles of pilA-N, omcE, omcS, omcT and omcZ for G. sulfurreducens in EET vary substantially, which also suggest that possession of PilA-N and multiple cytochromes of different structures enables G. sulfurreducens to mediate EET reactions efficiently with substrates of different properties.

Single-cell transcriptome analysis and protein profiling reveal broad immune system activation in IgG4-related disease.

IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with unclear pathogenesis. We performed single-cell RNA-seq and surface proteome analyses on 61,379 PBMCs from 9 treatment-naive IgG4-RD patients and 7 age- and sex-matched healthy controls. Integrative analyses were performed for altered gene expression in IgG4-RD, and flow cytometry and immunofluorescence were used for validation. We observed expansion of plasmablasts with enhanced protein processing and activation, which correlated with the number of involved organs in IgG4-RD. Increased proportions of CD4+ cytotoxic T lymphocytes (CTLs), CD8+ CTLs-GNLY (granulysin), and γδT cells with enhanced chemotaxis and cytotoxicity but with suppressed inhibitory receptors characterize IgG4-RD. Prominent infiltration of lymphocytes with distinct compositions were found in different organs of IgG4-RD patients. Transcription factors (TFs), including PRDM1/XBP1 and RUNX3, were upregulated in IgG4-RD, promoting the differentiation of plasmablasts and CTLs, respectively. Monocytes in IgG4-RD have stronger expression of genes related to cell adhesion and chemotaxis, which may give rise to profibrotic macrophages in lesions. The gene activation pattern in peripheral immune cells indicated activation of multiple interaction pathways between cell types, in part through chemokines or growth factors and their receptors. Specific upregulation of TFs and expansion of plasmablasts and CTLs may be involved in the pathogenesis of IgG4-RD, and each of these populations are candidate targets for therapeutic interventions in this disease.

Distinct microbial structure and metabolic potential shaped by significant environmental gradient impacted by ferrous slag weathering.

Alkaline ferrous slags pose global environmental issues and long-term risks to ambient environments. To explore the under-investigated microbial structure and biogeochemistry in such unique ecosystems, combined geochemical, microbial, ecological and metagenomic analyses were performed in the areas adjacent to a ferrous slag disposal plant in Sichuan, China. Different levels of exposure to ultrabasic slag leachate had resulted in a significant geochemical gradient of pH (8.0-12.4), electric potential (-126.9 to 437.9 mV), total organic carbon (TOC, 1.5-17.3 mg/L), and total nitrogen (TN, 0.17-1.01 mg/L). Distinct microbial communities were observed depending on their exposure to the strongly alkaline leachate. High pH and Ca2+ concentrations were associated with low microbial diversity and enrichment of bacterial classes Gamma-proteobacteria and Deinococci in the microbial communities exposed to the leachate. Combined metagenomic analyses of 4 leachate-unimpacted and 2-impacted microbial communities led to the assembly of one Serpentinomonas pangenome and 81 phylogenetically diversified metagenome assembled genomes (MAGs). The prevailing taxa in the leachate-impacted habitats (e.g., Serpentinomonas and Meiothermus spp.) were phylogenetically related to those in active serpentinizing ecosystems, suggesting the analogous processes between the man-made and natural systems. More importantly, they accounted for significant abundance of most functional genes associated with environmental adaptation and major element cycling. Their metabolic potential (e.g., cation/H+ antiporters, carbon fixation on lithospheric carbon source, and respiration coupling sulfur oxidization and oxygen or nitrate reduction) may support these taxa to survive and prosper in these unique geochemical niches. This study provides fundamental understandings of the adaptive strategies of microorganisms in response to the strong environmental perturbation by alkali tailings. It also contributes to a better comprehension of how to remediate environments affected by alkaline industrial material.

Enhancing electrical outputs of the fuel cells with Geobacter sulferreducens by overexpressing nanowire proteins.

Protein nanowires are critical electroactive components for electron transfer of Geobacter sulfurreducens biofilm. To determine the applicability of the nanowire proteins in improving bioelectricity production, their genes including pilA, omcZ, omcS and omcT were overexpressed in G. sulfurreducens. The voltage outputs of the constructed strains were higher than that of the control strain with the empty vector (0.470-0.578 vs. 0.355 V) in microbial fuel cells (MFCs). As a result, the power density of the constructed strains (i.e. 1.39-1.58 W m-2 ) also increased by 2.62- to 2.97-fold as compared to that of the control strain. Overexpression of nanowire proteins also improved biofilm formation on electrodes with increased protein amount and thickness of biofilms. The normalized power outputs of the constructed strains were 0.18-0.20 W g-1 that increased by 74% to 93% from that of the control strain. Bioelectrochemical analyses further revealed that the biofilms and MFCs with the constructed strains had stronger electroactivity and smaller internal resistance, respectively. Collectively, these results demonstrate for the first time that overexpression of nanowire proteins increases the biomass and electroactivity of anode-attached microbial biofilms. Moreover, this study provides a new way for enhancing the electrical outputs of MFCs.

Global occurrence of the bacteria with capability for extracellular reduction of iodate.

The γ-proteobacterium Shewanella oneidensis MR-1 reduces iodate to iodide extracellularly. Both dmsEFAB and mtrCAB gene clusters are involved in extracellular reduction of iodate by S. oneidensis MR-1. DmsEFAB reduces iodate to hypoiodous acid and hydrogen peroxide (H2O2). Subsequently, H2O2 is reduced by MtrCAB to facilitate DmsEFAB-mediated extracellular reduction of iodate. To investigate the distribution of bacteria with the capability for extracellular reduction of iodate, bacterial genomes were systematically searched for both dmsEFAB and mtrCAB gene clusters. The dmsEFAB and mtrCAB gene clusters were found in three Ferrimonas and 26 Shewanella species. Coexistence of both dmsEFAB and mtrCAB gene clusters in these bacteria suggests their potentials for extracellular reduction of iodate. Further analyses demonstrated that these bacteria were isolated from a variety of ecosystems, including the lakes, rivers, and subsurface rocks in East and Southeast Asia, North Africa, and North America. Importantly, most of the bacteria with both dmsEFAB and mtrCAB gene clusters were found in different marine environments, which ranged from the Arctic Ocean to Antarctic coastal marine environments as well as from the Atlantic Ocean to the Indian and Pacific Oceans. Widespread distribution of the bacteria with capability for extracellular reduction of iodate around the world suggests their significant importance in global biogeochemical cycling of iodine. The genetic organization of dmsEFAB and mtrCAB gene clusters also varied substantially. The identified mtrCAB gene clusters often contained additional genes for multiheme c-type cytochromes. The numbers of dmsEFAB gene cluster detected in a given bacterial genome ranged from one to six. In latter, duplications of dmsEFAB gene clusters occurred. These results suggest different paths for these bacteria to acquire their capability for extracellular reduction of iodate.

Concurrence of osteonecrosis and steroid myopathy secondary to oral steroid therapy in a patient with ABCB1 gene polymorphisms: A case report.

Glucocorticoids (GCs) are widely used in various autoimmune diseases. Side effects may occur in patients with long-term or high-dose GC usage. Among them, steroid myopathy and osteonecrosis are two severe forms. We report a patient with pemphigus vulgaris on GC-treatment who developed muscle weakness when a cumulative dose of methylprednisolone reached about 20g (14-80mg/d for 2.5 years). Laboratory tests showed slightly elevated lactate dehydrogenase and hydroxybutyrate dehydrogenase. MRI revealed osteonecrosis in the femoral head, distal femur, and proximal tibia of both legs. The biopsy of the right quadriceps revealed atrophy of type II myofiber without leukocyte infiltration, which was suggestive of steroid myopathy. Genotyping of the patient showed 5G/5G genotype of the PAI-1 gene and CC genotype of the ABCB1 gene (C3435T), suggesting she was sensitive to GCs. The patient's lesions were considered to be GC-induced adverse events, which were improved with tapering GC. Therefore, it is important to recognize steroid-induced musculoskeletal side effects and genotyping favors personalized medication.

The roles of DmsEFAB and MtrCAB in extracellular reduction of iodate by Shewanella oneidensis MR-1 with lactate as the sole electron donor.

To investigate their roles in extracellular reduction of iodate (IO3 - ) with lactate as an electron donor, the gene clusters of dmsEFAB, mtrCAB, mtrDEF and so4360-4357 in Shewanella oneidensis MR-1 were systematically deleted. Deletions of dmsEFAB and/or mtrCAB gene clusters diminished the bacterial ability to reduce IO3 - . Furthermore, DmsEFAB and MtrCAB worked collaboratively to reduce IO3 - of which DmsEFAB played a more dominant role than MtrCAB. MtrCAB was involved in detoxifying the reaction intermediate hydrogen peroxide (H2 O2 ). The reaction intermediate hypoiodous acid (HIO) was also found to inhibit microbial IO3 - reduction. SO4360-4357 and MtrDEF, however, were not involved in IO3 - reduction. Collectively, these results suggest a novel mechanism of extracellular reduction of IO3 - at molecular level, in which DmsEFAB reduces IO3 - to HIO and H2 O2 . The latter is further reduced to H2 O by MtrCAB to facilitate the DmsEFAB-mediated IO3 - reduction. The extracellular electron transfer pathway of S. oneidensis MR-1 is believed to mediate electron transfer from bacterial cytoplasmic membrane, across the cell envelope to the DmsEFAB and MtrCAB on the bacterial outer membrane.

Nutrition and clinical manifestations of pulmonary tuberculosis: A cross-sectional study in Shandong province, China.

BACKGROUND AND OBJECTIVES: The aim is to investigate the association between nutritional status and clinical picture of pulmonary tuberculosis (PTB). METHODS AND STUDY DESIGN: A total of 613 pulmonary tuberculosis patients in Weifang city, Shandong province, China were included. Clinical and nutritional history, anthropometry, nutritionally relevant indicators including serum total protein and albumin, hemoglobin and lymphocyte count were measured. Adjustments were made for confounders in multivariable logistic models where tuberculosis activity (clinical symptoms and signs, sputum-smear tests or chest computerized tomography (CT)) was the dependent variable. RESULTS: Hypoalbuminemia (OR=2.61; 95% CI, 1.69-4.03), anemia (OR=1.62; 95% CI, 1.04-2.51) and lymphocytopenia (OR=1.92; 95% CI, 1.21-3.05) were associated with a higher TB score (a clinical severity measure for pulmonary tuberculosis based on typical signs and symptoms); hypoalbuminemia (OR=1.75; 95% CI, 1.08-2.84) and anemia (OR=1.87; 95% CI, 1.14-3.08) were associated with a positive sputum smear; anemia (OR=3.58; 95% CI, 1.85-6.94) was associated with cavitation in CT. CONCLUSIONS: Hypoalbuminemia, anemia and lymphocytopenia were positively associated with the severity of clinical manifestation of PTB. Nutritional status may be a marker for the severity of the clinical manifestations of PTB.

Biofilm Biology and Engineering of Geobacter and Shewanella spp. for Energy Applications.

Geobacter and Shewanella spp. were discovered in late 1980s as dissimilatory metal-reducing microorganisms that can transfer electrons from cytoplasmic respiratory oxidation reactions to external metal-containing minerals. In addition to mineral-based electron acceptors, Geobacter and Shewanella spp. also can transfer electrons to electrodes. The microorganisms that have abilities to transfer electrons to electrodes are known as exoelectrogens. Because of their remarkable abilities of electron transfer, Geobacter and Shewanella spp. have been the two most well studied groups of exoelectrogens. They are widely used in bioelectrochemical systems (BESs) for various biotechnological applications, such as bioelectricity generation via microbial fuel cells. These applications mostly associate with Geobacter and Shewanella biofilms grown on the surfaces of electrodes. Geobacter and Shewanella biofilms are electrically conductive, which is conferred by matrix-associated electroactive components such as c-type cytochromes and electrically conductive nanowires. The thickness and electroactivity of Geobacter and Shewanella biofilms have a significant impact on electron transfer efficiency in BESs. In this review, we first briefly discuss the roles of planktonic and biofilm-forming Geobacter and Shewanella cells in BESs, and then review biofilm biology with the focus on biofilm development, biofilm matrix, heterogeneity in biofilm and signaling regulatory systems mediating formation of Geobacter and Shewanella biofilms. Finally, we discuss strategies of Geobacter and Shewanella biofilm engineering for improving electron transfer efficiency to obtain enhanced BES performance.

Serum Uric Acid Concentrations and Risk of Adverse Outcomes in Patients With COVID-19.

Background: Although hyperuricemia frequently associates with respiratory diseases, patients with severe coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) can show marked hypouricemia. Previous studies on the association of serum uric acid with risk of adverse outcomes related to COVID-19 have produced contradictory results. The precise relationship between admission serum uric acid and adverse outcomes in hospitalized patients is unknown. Methods: Data of patients affected by laboratory-confirmed COVID-19 and admitted to Leishenshan Hospital were retrospectively analyzed. The primary outcome was composite and comprised events, such as intensive care unit (ICU) admission, mechanical ventilation, or mortality. Logistic regression analysis was performed to explore the association between serum concentrations of uric acid and the composite outcome, as well as each of its components. To determine the association between serum uric acid and in-hospital adverse outcomes, serum uric acid was also categorized by restricted cubic spline, and the 95% confidence interval (CI) was used to estimate odds ratios (OR). Results: The study cohort included 1854 patients (mean age, 58 years; 52% women). The overall mean ± SD of serum levels of uric acid was 308 ± 96 µmol/L. Among them, 95 patients were admitted to ICU, 75 patients received mechanical ventilation, and 38 died. In total, 114 patients reached composite end-points (have either ICU admission, mechanical ventilation or death) during hospitalization. Compared with a reference group with estimated baseline serum uric acid of 279-422 µmol/L, serum uric acid values ≥ 423 µmol/L were associated with an increased risk of composite outcome (OR, 2.60; 95% CI, 1.07- 6.29) and mechanical ventilation (OR, 3.01; 95% CI, 1.06- 8.51). Serum uric acid ≤ 278 µmol/L was associated with an increased risk of the composite outcome (OR, 2.07; 95% CI, 1.18- 3.65), ICU admission (OR, 2.18; 95% CI, 1.17- 4.05]), and mechanical ventilation (OR, 2.13; 95% CI, 1.06- 4.28), as assessed by multivariate analysis. Conclusions: This study shows that the association between admission serum uric acid and composite outcome of COVID-19 patients was U-shaped. In particular, we found that compared with baseline serum uric acid levels of 279-422 µmol/L, values ≥ 423 µmol/L were associated with an increased risk of composite outcome and mechanical ventilation, whereas levels ≤ 278 µmol/L associated with increased risk of composite outcome, ICU admission and mechanical ventilation.

Increased meat consumption is associated with reduced tuberculosis treatment failure rate: A cohort study.

BACKGROUND AND OBJECTIVES: Information regarding the relationship between dietary meat intake and tuberculosis treatment outcomes among patients with tuberculosis is still limited. The aim of the present study was to investigate the relationship between meat consumption and tuberculosis treatment outcomes in patients with pulmonary tuberculosis. METHODS AND STUDY DESIGN: A pulmonary tuberculosis cohort study including 2,261 patients with pulmonary tuberculosis was conducted in Linyi, Shandong Province, China from 2009 to 2013. Dietary data were collected using a semi-quantitative food frequency questionnaire. Treatment outcomes were assessed using a combination of sputum smear microscopy and chest computerized tomography. RESULTS: In a multiple adjusted model, the higher quartile of total meat (OR=0.59, 95% CI, 0.38-0.91) was associated with a decreased failure rate of pulmonary tuberculosis treatment. In addition, higher consumption of chicken (OR=0.62; 95% CI, 0.44-0.87) and pork (OR=0.54; 95% CI, 0.31-0.95) was associated with a lower failure rate of tuberculosis treatment. CONCLUSIONS: Increased dietary intake of total meat, pork, and chicken are associated with a decreased failure rate of pulmonary tuberculosis treatment. A higher dietary meat intake may be beneficial in pulmonary tuberculosis treatment.

Vitamins A and D fail to protect against tuberculosis-drug-induced liver injury: A post hoc analysis of a previous randomized controlled trial.

OBJECTIVES: Vitamins A and D provided protection from xenobiotic-induced liver injury in previous animal studies. We conducted a post hoc analysis of our previous randomized controlled trial to investigate the effects of vitamin A and D supplementation on tuberculosis-drug-induced liver injury. METHODS: The trial was conducted in a hospital in Qingdao, China, from October 2012 to March, 2015. The control group received only tuberculosis treatment. The vitamin A, vitamin D, and vitamins A & D groups received, respectively, additional supplementation of 2000 IU/d vitamin A, 400 IU/d vitamin D, and a combination of 2000 IU/d vitamin A and 400 IU/d vitamin D. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, γ-glutamyltransferase, and cholinesterase were monitored throughout the treatment. Liver injury was defined as ALT or AST three times higher than the upper limit of normal, which was defined for AST, ALT, alkaline phosphatase, γ-glutamyltransferase, and cholinesterase, respectively, as 40 U/L, 40 U/L, 150 U/L, 40 U/L, and 10 500 U/L. RESULTS: Among the 753 participants, 11% exhibited liver injury. No significant effect of vitamin A or D supplementation was observed on the incidence of liver injury or on elevated liver indices including ALT, AST, alkaline phosphatase, γ-glutamyltransferase, and cholinesterase. The interaction between vitamin A and D supplementation was not significant. CONCLUSIONS: Vitamin A and D supplementation did not protect against tuberculosis-drug-induced liver injury. Future work should evaluate the effects of higher dosages of vitamins A and D and the effects of different genotypes for vitamin A and D metabolic enzymes or receptors.

Shewanella biofilm development and engineering for environmental and bioenergy applications.

The genus Shewanella comprises about 70 species of Gram-negative, facultative anaerobic bacteria inhabiting various environments, which have shown great potential in various biotechnological applications ranging from environmental bioremediation, metal(loid) recovery and material synthesis to bioenergy generation. Most environmental and energy applications of Shewanella involve the biofilm mode of growth on surfaces of solid minerals or electrodes. In this article, we first provide an overview of Shewanella biofilm biology with the focus on biofilm dynamics, biofilm matrix, and key signalling systems involved in Shewanella biofilm development. Then we review strategies recently exploited to engineer Shewanella biofilms to improve biofilm-mediated bioprocesses.

Optogenetic Modulation of a Catalytic Biofilm for the Biotransformation of Indole into Tryptophan.

In green chemical synthesis, biofilms as biocatalysts have shown great promise. Efficient biofilm-mediated biocatalysis requires the modulation of biofilm formation. Optogenetic tools are ideal to control biofilms because light is noninvasive, easily controllable, and cost-efficient. In this study, a gene circuit responsive to near-infrared (NIR) light was used to modulate the cellular level of bis-(3'-5') cyclic dimeric guanosine monophosphate (c-di-GMP), a central regulator of the prokaryote biofilm lifestyle, which allowed the regulation of biofilm formation by using NIR light. The engineered biofilm was applied to catalyze the biotransformation of indole into tryptophan in submerged biofilm reactors and NIR-light-enhanced biofilm formation resulted in an approximately 30 % increase in tryptophan yield, which demonstrates the feasibility of the application of light to modulate the formation and performance of catalytic biofilms for chemical production. The c-di-GMP-targeted optogenetic approach to modulate catalytic biofilms showcases applications for biofilm-mediated biocatalysis.

Engineering a light-responsive, quorum quenching biofilm to mitigate biofouling on water purification membranes.

Quorum quenching (QQ) has been reported to be a promising approach for membrane biofouling control. Entrapment of QQ bacteria in porous matrices is required to retain them in continuously operated membrane processes and to prevent uncontrollable biofilm formation by the QQ bacteria on membrane surfaces. It would be more desirable if the formation and dispersal of biofilms by QQ bacteria could be controlled so that the QQ bacterial cells are self-immobilized, but the QQ biofilm itself still does not compromise membrane performance. In this study, we engineered a QQ bacterial biofilm whose growth and dispersal can be modulated by light through a dichromatic, optogenetic c-di-GMP gene circuit in which the bacterial cells sense near-infrared (NIR) light and blue light to adjust its biofilm formation by regulating the c-di-GMP level. We also demonstrated the potential application of the engineered light-responsive QQ biofilm in mitigating biofouling of water purification forward osmosis membranes. The c-di-GMP-targeted optogenetic approach for controllable biofilm development we have demonstrated here should prove widely applicable for designing other controllable biofilm-enabled applications such as biofilm-based biocatalysis.

Harnessing the Periplasm of Bacterial Cells To Develop Biocatalysts for the Biosynthesis of Highly Pure Chemicals.

Although biocatalytic transformation has shown great promise in chemical synthesis, there remain significant challenges in controlling high selectivity without the formation of undesirable by-products. For instance, few attempts to construct biocatalysts for de novo synthesis of pure flavin mononucleotide (FMN) have been successful, due to riboflavin (RF) accumulating in the cytoplasm and being secreted with FMN. To address this problem, we show here a novel biosynthesis strategy, compartmentalizing the final FMN biosynthesis step in the periplasm of an engineered Escherichia coli strain. This construct is able to overproduce FMN with high specificity (92.4% of total excreted flavins). Such a biosynthesis approach allows isolation of the final biosynthesis step from the cytoplasm to eliminate undesirable by-products, providing a new route to develop biocatalysts for the synthesis of high-purity chemicals.IMPORTANCE The periplasm of Gram-negative bacterial hosts is engineered to compartmentalize the final biosynthesis step from the cytoplasm. This strategy is promising for the overproduction of high-value products with high specificity. We demonstrate the successful implementation of this strategy in microbial production of highly pure FMN.

A near-infrared light responsive c-di-GMP module-based AND logic gate in Shewanella oneidensis.

A novel, biofilm-based AND logic gate was constructed in Shewanella oneidensis through a near-infrared (NIR) light responsive c-di-GMP module. The logic gate was demonstrated in microbial fuel cells with isopropyl ß-d-thiogalactoside (IPTG) and NIR light as the inputs and electrical signals as the output.