Association between the American Heart Association's new "Life's Essential 8" metrics and kidney stone.

PURPOSE: The incidence of kidney stone disease has increased worldwide, resulting in high medical costs and social burden. Kidney stone disease shares some common features with the risk factors of cardiovascular diseases (CVDs). We investigated the association between cardiovascular health (CVH) based on the Life's Essential 8 (LE8) score developed by the American Heart Association and the incidence of kidney stone disease. METHODS: We analyzed the data of 29,469 US adults aged 20 years or above from the National Health and Nutrition Examination Survey, 2007-2018. According to the LE8 score, CVH was divided into three categories: poor, intermediate, and ideal. Logistic regression was used to determine the association between CVH and the incidence of kidney stone disease by estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The average age of the participants was 48.6 years, and 50% of the participants were women. The numbers of participants with poor, intermediate, and ideal CVH were 4149, 19,782, and 5538, respectively. After adjusting for related confounding factors, ideal CVH was associated with a reduction in the odds of kidney stone occurrence as compared to poor CVH (adjusted OR [aOR]: 0.45, 95% CI: 0.35-0.57, p < 0.001). Moreover, if the ideal CVH metrics was ≥ 6, the odds of kidney stone occurrence decreased by up to 61% (aOR: 0.39, 95% CI: 0.30-0.51). CONCLUSIONS: In the present study, ideal CVH, a factor indicative of a healthy lifestyle, was associated with lower odds of kidney stone occurrence.

The influence of Life's Essential 8 on the link between socioeconomic status and depression in adults: a mediation analysis.

BACKGROUND: Individuals with low socioeconomic status (SES) are at a higher risk of developing depression. However, evidence on the role of cardiovascular health (CVH) in this chain is sparse and limited. The purpose of this research was to assess the mediating role of Life's Essential 8 (LE8), a recently updated measurement of CVH, in the association between SES and depression according to a nationally representative sample of adults. METHODS: Data was drawn from the National Health and Nutrition Examination Survey (NHANES) in 2013-2018. Multivariate logistic regression analysis was applied to analyze the association of SES (measured via the ratio of family income to poverty (FIPR), occupation, educational level, and health insurance) and LE8 with clinically relevant depression (CRD) (evaluated using the Patient Health Questionnaire (PHQ-9)). Multiple linear regression analysis was performed to analyze the correlation between SES and LE8. Mediation analysis was carried out to explore the mediating effect of LE8 on the association between SES and CRD. Moreover, these associations were still analyzed by sex, age, and race. RESULTS: A total of 4745 participants with complete PHQ-9 surveys and values to calculated LE8 and SES were included. In the fully adjusted model, individuals with high SES had a significantly higher risk of CRD (odds ratio = 0.21; 95% confidence interval: 0.136 to 0.325, P < 0.01) compared with those with low SES. Moreover, LE8 was estimated to mediate 22.13% of the total association between SES and CRD, and the mediating effect of LE8 varied in different sex and age groups. However, the mediating effect of LE8 in this chain was significant in different sex, age, and racial subgroups except for Mexican American (MA) individuals. CONCLUSION: The results of our study suggest that LE8 could mediate the association between SES and CRD. Additionally, the mediating effect of LE8 in this chain could be influenced by the race of participants.

Efficient Precoding and Power Allocation Techniques for Maximizing Spectral Efficiency in Beamspace MIMO-NOMA Systems.

Beamspace MIMO-NOMA is an effective way to improve spectral efficiency. This paper focuses on a downlink non-orthogonal multiple access (NOMA) transmission scheme for a beamspace multiple-input multiple-output (MIMO) system. To increase the sum rate, we jointly optimize precoding and power allocation, which presents a non-convex problem. To solve this difficulty, we employ an alternating algorithm to optimize the precoding and power allocation. Regarding the precoding subproblem, we demonstrate that the original optimization problem can be transformed into an unconstrained optimization problem. Drawing inspiration from fraction programming (FP), we reconstruct the problem and derive a closed-form expression of the optimization variable. In addition, we effectively reduce the complexity of precoding by utilizing Neumann series expansion (NSE). For the power allocation subproblem, we adopt a dynamic power allocation scheme that considers both the intra-beam power optimization and the inter-beam power optimization. Simulation results show that the energy efficiency of the proposed beamspace MIMO-NOMA is significantly better than other conventional schemes.

Multifunctional Hollow MnO2 @Porphyrin@Bromelain Nanoplatform for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) has been showing great potential in cancer treatment. However, the efficacy of PDT is always limited by the intrinsic hypoxic tumor microenvironment (TME) and the low accumulation efficiency of photosensitizers in tumors. To address the issue, a multifunctional hollow multilayer nanoplatform (H-MnO2 @TPyP@Bro) comprising manganese dioxide, porphyrin (TPyP) and bromelain (Bro), is developed for enhanced photodynamic therapy. MnO2 catalyzes the intracellular hydrogen peroxide (H2 O2 ) to produce oxygen (O2 ), reversing the hypoxic TME in vivo. The generated O2 is converted into singlet oxygen (1 O2 ) by the TPyP shell under near-infrared light, which can inhibit tumor proliferation. Meanwhile, the Bro can digest collagen in the extracellular matrix around the tumor, and can promote the accumulation of H-MnO2 @TPyP@Bro in the deeper tumor tissue, further improving the therapeutic effect of PDT. In addition, MnO2 can react with the overexpressed glutathione in TME to release Mn2+ . Consequently, Mn2+ not only induces chemo-dynamic therapy based on Fenton reaction by converting H2 O2 into hydroxyl radicals, but also activates the Mn2+ -based magnetic resonance imaging. Therefore, the developed H-MnO2 @TPyP@Bro nanoplatform can effectively modulate the unfavorable TME and overcome the limitations of conventional PDT for cancer diagnostic and therapeutic.

A Cyanine-Mediated Self-Assembly System for the Construction of a Two-in-One Nanodrug.

The combination of gene therapy and chemotherapy provides a We developed a simple and versatile approach to prepare a series of two-in-one nanodrugs through direct self-assembly of cyanine-labeled single-stranded DNA (Cys-DNA) and different types of drug molecules. Molecular dynamics simulation showed that the Cys introduced into the DNA could enhance the noncovalent interaction between Cys-DNA and drug molecules. More drug molecules were incorporated into Cys-DNA, tending to spontaneously form hybrid Cys-DNA/drug nanosphere. Such nanospheres serve as both carriers and cargoes, excluding the extra use of nontherapeutic excipients and showing ultrahigh drug loading capacity. Following this approach, an antisense oligonucleotides/doxorubicin nanodrug model was constructed, demonstrating the significant synergistic anti-tumor therapeutic effect. As a proof of the concept, our study establishes a simple and reproducible two-in-one nucleic acid-based drug formulation.

Irisin ameliorates high glucose-induced cardiomyocytes injury via AMPK/mTOR signal pathway.

High glucose (HG)-induced cardiomyocytes (CMs) injury is a leading cause of diabetic cardiomyopathy with little treatment options. Irisin, a new myokine, which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), has aroused great attention as an essential cardioprotective factor and glucose metabolism regulator but little was known on diabetic cardiomyopathy yet. Here, we aim to clarify the role of irisin in the HG-induced CMs injury. Neonatal Sprague-Dawley rat CMs were cultured in a normal or HG medium for 12, 24, and 48 hr, respectively before exposing to irisin. The apoptosis level was determined by terminal-deoxynucleotidyl transferase-mediated-dUTP nick end-labeling assay. Cell viability was measured with the conventional methyl thiazolyl tetrazolium assay. Moreover, reactive oxygen species production was evaluated by dihydroethidium staining. Inflammatory factors, namely tumor necrosis factor-α, interleukin-6, interleukin-1ß were determined by enzyme-linked immunosorbent assay kits. Furthermore, protein and messenger RNA (mRNA) expressions were measured by western blot and quantitative real-time polymerase chain reaction, respectively. HG increases the apoptosis of CMs and activated the inflammatory responses and oxidative stress in CMs. Meanwhile, the mRNA and protein expressions of FNDC5 are decreased after HG exposure. Nevertheless, the increased apoptosis is alleviated by irisin treatment. Notably, irisin suppresses the inflammatory responses and oxidative stress in injured CMs. Mechanically, after the administration of Compound C, AMP-activated protein kinase (AMPK) inhibitor, these cardioprotective effects resulting from irisin are reversed. Irisin plays a significant role in antiapoptosis, anti-inflammation, antioxidative stress in HG-induced CMs via AMPK/mammalian target of the rapamycin signaling pathway.

Metabolic engineering of Escherichia coli for production of chemicals derived from the shikimate pathway.

The shikimate pathway is indispensable for the biosynthesis of natural products with aromatic moieties. These products have wide current and potential applications in food, cosmetics and medicine, and consequently have great commercial value. However, compounds extracted from various plants or synthesized from petrochemicals no longer satisfy the requirements of contemporary industries. As a result, an increasing number of studies has focused on this pathway to enable the biotechnological manufacture of natural products, especially in E. coli. Furthermore, the development of synthetic biology, systems metabolic engineering and high flux screening techniques has also contributed to improving the biosynthesis of high-value compounds based on the shikimate pathway. Here, we review approaches based on a combination of traditional and new metabolic engineering strategies to increase the metabolic flux of the shikimate pathway. In addition, applications of this optimized pathway to produce aromatic amino acids and a range of natural products is also elaborated. Finally, this review sums up the opportunities and challenges facing this field.

Genetic engineering of Escherichia coli to improve L-phenylalanine production.

BACKGROUND: L-phenylalanine (L-Phe) is an essential amino acid for mammals and applications expand into human health and nutritional products. In this study, a system level engineering was conducted to enhance L-Phe biosynthesis in Escherichia coli. RESULTS: We inactivated the PTS system and recruited glucose uptake via combinatorial modulation of galP and glk to increase PEP supply in the Xllp01 strain. In addition, the HTH domain of the transcription factor TyrR was engineered to decrease the repression on the transcriptional levels of L-Phe pathway enzymes. Finally, proteomics analysis demonstrated the third step of the SHIK pathway (catalyzed via AroD) as the rate-limiting step for L-Phe production. After optimization of the aroD promoter strength, the titer of L-Phe increased by 13.3%. Analysis of the transcriptional level of genes involved in the central metabolic pathways and L-Phe biosynthesis via RT-PCR showed that the recombinant L-Phe producer exhibited a great capability in the glucose utilization and precursor (PEP and E4P) generation. Via systems level engineering, the L-Phe titer of Xllp21 strain reached 72.9 g/L in a 5 L fermenter under the non-optimized fermentation conditions, which was 1.62-times that of the original strain Xllp01. CONCLUSION: The metabolic engineering strategy reported here can be broadly employed for developing genetically defined organisms for the efficient production of other aromatic amino acids and derived compounds.

Rational design and analysis of an Escherichia coli strain for high-efficiency tryptophan production.

L-tryptophan (L-trp) is a precursor of various bioactive components and has great pharmaceutical interest. However, due to the requirement of several precursors and complex regulation of the pathways involved, the development of an efficient L-trp production strain is challenging. In this study, Escherichia coli (E. coli) strain KW001 was designed to overexpress the L-trp operator sequences (trpEDCBA) and 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (aroG fbr ). To further improve the production of L-trp, pyruvate kinase (pykF) and the phosphotransferase system HPr (ptsH) were deleted after inactivation of repression (trpR) and attenuation (attenuator) to produce strain KW006. To overcome the relatively slow growth and to increase the transport rate of glucose, strain KW018 was generated by combinatorial regulation of glucokinase (galP) and galactose permease (glk) expression. To reduce the production of acetic acid, strain KW023 was created by repressive regulation of phosphate acetyltransferase (pta) expression. In conclusion, strain KW023 efficiently produced 39.7 g/L of L-trp with a conversion rate of 16.7% and a productivity of 1.6 g/L/h in a 5 L fed-batch fermentation system.

Determination of key enzymes for threonine synthesis through in vitro metabolic pathway analysis.

BACKGROUND: The overexpression of key enzymes in a metabolic pathway is a frequently used genetic engineering strategy for strain improvement. Metabolic control analysis has been proposed to quantitatively determine key enzymes. However, the lack of quality data often makes it difficult to correctly identify key enzymes through control analysis. Here, we proposed a method combining in vitro metabolic pathway analysis and proteomics measurement to find the key enzymes in threonine synthesis pathway. RESULTS: All enzymes in the threonine synthesis pathway were purified for the reconstruction and perturbation of the in vitro pathway. Label-free proteomics technology combined with APEX (absolute protein expression measurements) data analysis method were employed to determine the absolute enzyme concentrations in the crude enzyme extract obtained from a threonine production strain during the fastest threonine production period. The flux control coefficient of each enzyme in the pathway was then calculated by measuring the flux changes after titration of the corresponding enzyme. The isoenzyme LysC catalyzing the first step in the pathway has the largest flux control coefficient, and thus its concentration change has the biggest impact on pathway flux. To verify that the key enzyme identified through in vitro pathway analysis is also the key enzyme in vivo, we overexpressed LysC in the original threonine production strain. Fermentation results showed that the threonine concentration was increased 30% and the yield was increased 20%. CONCLUSIONS: In vitro metabolic pathways simulating in vivo cells can be built based on precise measurement of enzyme concentrations through proteomics technology and used for the determination of key enzymes through metabolic control analysis. This provides a new way to find gene overexpression targets for industrial strain improvement.

Developing a high-throughput screening method for threonine overproduction based on an artificial promoter.

BACKGROUND: L-Threonine is an important amino acid for animal feed. Though the industrial fermentation technology of threonine achieved a very high level, there is still significant room to further improve the industrial strains. The biosensor-based high-throughput screening (HTS) technology has demonstrated its powerful applications. Unfortunately, for most of valuable fine chemicals such as threonine, a HTS system has not been established mainly due to the absence of a suitable biosensor. In this study, we developed a HTS method to gain high-yielding threonine-producing strains. RESULTS: Novel threonine sensing promoters including cysJp and cysHp were discovered by proteomic analyses of Escherichia coli in response to extracellular threonine challenges. The HTS method was constructed using a device composed of the fused cysJp and cysHp as a promoter and a linked enhanced green fluorescent protein gene as a reporter. More than 400 strains were selected with fluorescence activated cell sorting technology from a library of 20 million mutants and tested within 1 week. Thirty-four mutants have higher productivities than the starting industrial producer. One mutant produced 17.95 % more threonine in a 5-L jar fermenter. CONCLUSIONS: This method should play a functional role for continuous improvement of threonine industry. Additionally, the threonine sensor construction using promoters obtained by proteomics analyses is so convenient that it would be easily extended to develop HTS models for other biochemicals.

Compression of EEG signals with the LSTM-autoencoder via domain adaptation approach.

The successful implementation of neural network-based EEG signal compression has led to significant cost reductions in data transmission. However, a major obstacle in this process arises from the decline in performance when compressing EEG signals from multiple subjects. This challenge arises due to the notable feature shift of EEG signals between subjects, which poses an impediment to the neural network's efficient concurrent acquisition of information from multiple subjects. To address this limitation and enable more effective utilization of data for improving the performance on target domain, we propose a Domain Adaptation (DA) framework based on LSTM-autoencoder. Our experiments encompassed the following: (1) A comparison between LSTM-autoencoder, GRU-autoencoder, and the commonly used convolutional autoencoder (CAE) in EEG compression. (2) A comparison between our proposed DA method and the MMD-based DA method, as well as Fine-tuning transfer learning. The results demonstrate the following: (1) LSTM-autoencoder outperforms other models in both subject-specific and cross-subject scenarios. (2) Using transfer learning improves the performance of LSTM-autoencoder on the target subject. (3) Our proposed method outperforms maximum mean discrepancy (MMD)-based domain adaptation and fine-tuning approaches, resulting in a more significant enhancement.

Advances in the Pathogenesis of Steroid-Associated Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic condition characterized by bone cell ischemia, necrosis, bone trabecular fracture, and clinical symptoms such as pain, femoral head collapse, and joint dysfunction that can lead to disability. The disability rate of ONFH is very high, which imposes a significant economic burden on both families and society. Steroid-associated osteonecrosis of the femoral head (SANFH) is the most common type of ONFH. However, the pathogenesis of SANFH remains unclear, and it is an urgent challenge for orthopedic surgeons to explore it. In this paper, the pathogenesis of SANFH and its related signaling pathways were briefly reviewed to enhance comprehension of the pathogenesis and prevention of SANFH.

A super-hydrophilic graphite directly from lignin enabled by a room-temperature cascade catalytic carbonization.

A cost-effective, and low-energy room-temperature cascade catalytic carbonization strategy is demonstrated for converting lignin into graphite with a high yield of 87 %, a high surface potential of -37 eV and super-hydrophilicity. This super-hydrophilic feature endows the lignin-derived graphite to be dispersed in a variety of polar solvents, which is important for its future applications. Encapsulating of liquid metals with the graphite for electrical circuit patterning on flexible substrates is also advocated. These written patterns show superb conductivity of 4.9 × 106 S/m, offering good performance stability and reliability while being repeatedly stretched, folded, twisted, and bent. This will offer new designs for flexible electronic devices, sensors, and biomedical devices.

mRNA-responsive two-in-one nanodrug for enhanced anti-tumor chemo-gene therapy.

The combination of chemotherapy and gene therapy holds great promise for the treatment and eradication of tumors. However, due to significant differences in physicochemical properties between chemotherapeutic agents and functional nucleic acid drugs, direct integration into a single nano-agent is hindered, impeding the design and construction of an effective co-delivery nano-platform for synergistic anti-tumor treatments. In this study, we have developed an mRNA-responsive two-in-one nano-drug for effective anti-tumor therapy by the direct self-assembly of 2'-fluoro-substituted antisense DNA against P-glycoprotein (2'F-DNA) and chemo drug paclitaxel (PTX). The 2'-fluoro modification of DNA could significantly increase the interaction between the therapeutic nucleic acid and the chemotherapeutic drug, promoting the successful formation of 2'F-DNA/PTX nanospheres (2'F-DNA/PTX NSs). Due to the one-step self-assembly process without additional carrier materials, the prepared 2'F-DNA/PTX NSs exhibited considerable loading efficiency and bioavailability of PTX. In the presence of endogenous P-glycoprotein mRNA, the 2'F-DNA/PTX NSs were disassembled. The released 2'F-DNA could down-regulate the expression of P-glycoprotein, which decreased the multidrug resistance of tumor cells and enhanced the chemotherapy effect caused by PTX. In this way, the 2'F-DNA/PTX NSs could synergistically induce the apoptosis of tumor cells and realize the combined anti-tumor therapy. This strategy might provide a new tool to explore functional intracellular co-delivery nano-systems with high bioavailability and exhibit potential promising in the applications of accurate diagnosis and treatment of tumors.

The weekend effect in kidney transplantation outcomes: A meta-analysis.

OBJECTIVE: To determine whether kidney transplants performed during weekends have worse outcomes than those performed during weekdays. METHODS: For this systematic review, PubMed, EMBASE, and the Cochrane Library (January 2000 to January 2023) were searched. We examined the survival rates of patients and grafts for hospital inpatients admitted during weekends and those admitted during weekdays. To be included, the study had to be in English and had to provide discrete survival data around weekends versus weekdays, including patients who were admitted as inpatients over the weekend. RESULTS: Five studies (n = 163,506 patients) were examined. The hazards ratio (HR) of the survival rate of patients with weekend transplantation was 1.01 (95% confidence interval [CI], 0.96 to 1.06) when compared with patients with weekday transplantation. Patients who had renal transplant on weekends had an overall allograft survival HR of 1.01 (95% CI, 0.99 to 1.03) and death-censored allograft survival HR of 1.01 (95% CI, 0.98 to 1.04). Comparison of length of hospital stay, rejection, surgical complications, and vascular complications between renal transplants on weekends and those on weekdays showed no statistical difference. CONCLUSION: Hospital inpatients admitted for renal transplantation during weekends have a survival rate similar to that of inpatients admitted during weekdays. The weekend effect of renal transplantation was very weak; hence, transplantations done during weekends and weekdays are both appropriate.

Advanced bioactive nanomaterials for diagnosis and treatment of major chronic diseases.

With the rapid innovation of nanoscience and technology, nanomaterials have also been deeply applied in the medical and health industry and become one of the innovative methods to treat many diseases. In recent years, bioactive nanomaterials have attracted extensive attention and have made some progress in the treatment of some major chronic diseases, such as nervous system diseases and various malignant tumors. Bioactive nanomaterials depend on their physical and chemical properties (crystal structure, surface charge, surface functional groups, morphology, and size, etc.) and direct produce biological activity and play to the role of the treatment of diseases, compared with the traditional nanometer pharmaceutical preparations, biological active nano materials don't exert effects through drug release, way more directly, also is expected to be more effective for the treatment of diseases. However, further studies are needed in the evaluation of biological effects, fate in vivo, structure-activity relationship and clinical transformation of bionanomaterials. Based on the latest research reports, this paper reviews the application of bioactive nanomaterials in the diagnosis and treatment of major chronic diseases and analyzes the technical challenges and key scientific issues faced by bioactive nanomaterials in the diagnosis and treatment of diseases, to provide suggestions for the future development of this field.

The role of periodontitis in the link between alpha-tocopherol intake and cognitive performance: A mediation analysis in older adults.

Background: Epidemiological evidence on alpha (α)-tocopherol intake and cognitive performance in older individuals is controversial and the effect of periodontitis in this chain is sparse and limited. The goal of this study was to characterize the association between α-tocopherol intake and cognitive performance and the mediating role of periodontitis in a nationally representative sample of older adults. Methods: Data from the National Health and Nutrition Examination Survey (NHANES), 2011-2014, were used. Multivariate logistic regression analysis was performed to explore the association of α-tocopherol intake, periodontal measures (mean attachment loss [AL] and mean probing depth [PD]), and clinical periodontitis defined by the European Workshop in Periodontology with poor cognitive performance evaluated by Consortium to Establish a Registry for Alzheimer's disease (CERAD); the animal fluency test (AFT); and the Digit Symbol Substitution test (DSST) and the correlation between α-tocopherol intake and clinical periodontitis. Multiple linear regression analysis was used to explore the relationship between α-tocopherol intake and periodontal measures. Mediation analysis was used to test the effects of periodontal measures on the association between α-tocopherol intake and cognitive measures. Results: A total of 1,749 older participants (≥60 years of age) with complete periodontal diagnosis, dietary retrospective survey, and cognitive tests were included. In the fully adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of CERAD score, AFT score and DSST score were 0.214 (0.137-0.327), 0.378 (0.241-0.585) and 0.298 (0.169-0.512) for the highest versus lowest tertile of α-tocopherol intake, respectively. And participants with clinical periodontitis were more likely to exhibit lower DSST score (OR = 1.689; 95 CI%: 1.018-2.771) than those without periodontitis. Mean AL (OR = 1.296; 95 CI%: 1.102-1.524) and PD (OR = 1.667; 95 CI%: 1.18-2.363) were negatively correlated with DSST, and were estimated to mediate 9.1 and 8.2% of the total association between α-tocopherol intake and cognitive performance, respectively. Conclusion: Finding of the present study suggested that participants with low α-tocopherol intake were at higher risk for developing cognitive decline. Moreover, periodontitis mediated the association between α-tocopherol intake and cognitive performance.

Design, Evaluation, and Implementation of Synthetic Isopentyldiol Pathways in Escherichia coli.

Isopentyldiol (IPDO) is an important raw material in the cosmetic industry. So far, IPDO is exclusively produced through chemical synthesis. Growing interest in natural personal care products has inspired the quest to develop a biobased process. We previously reported a biosynthetic route that produces IPDO via extending the leucine catabolism (route A), the efficiency of which, however, is not satisfactory. To address this issue, we computationally designed a novel non-natural IPDO synthesis pathway (route B) using RetroPath RL, the state-of-the-art tool for bioretrosynthesis based on artificial intelligence methods. We compared this new pathway with route A and two other intuitively designed routes for IPDO biosynthesis from various perspectives. Route B, which exhibits the highest thermodynamic driving force, least non-native reaction steps, and lowest energy requirements, appeared to hold the greatest potential for IPDO production. All three newly designed routes were then implemented in the Escherichia coli BL21(DE3) strain. Results show that the computationally designed route B can produce 2.2 mg/L IPDO from glucose but no IPDO production from routes C and D. These results highlight the importance and usefulness of in silico design and comprehensive evaluation of the potential efficiencies of candidate pathways in constructing novel non-natural pathways for the production of biochemicals.

Biosynthesizing structurally diverse diols via a general route combining oxidative and reductive formations of OH-groups.

Diols encompass important bulk and fine chemicals for the chemical, pharmaceutical and cosmetic industries. During the past decades, biological production of C3-C5 diols from renewable feedstocks has received great interest. Here, we elaborate a general principle for effectively synthesizing structurally diverse diols by expanding amino acid metabolism. Specifically, we propose to combine oxidative and reductive formations of hydroxyl groups from amino acids in a thermodynamically favorable order of four reactions catalyzed by amino acid hydroxylase, L-amino acid deaminase, α-keto acid decarboxylase and aldehyde reductase consecutively. The oxidative formation of hydroxyl group from an alkyl group is energetically more attractive than the reductive pathway, which is exclusively used in the synthetic pathways of diols reported so far. We demonstrate this general route for microbial production of branched-chain diols in E. coli. Ten C3-C5 diols are synthesized. Six of them, namely isopentyldiol (IPDO), 2-methyl-1,3-butanediol (2-M-1,3-BDO), 2-methyl-1,4-butanediol (2-M-1,4-BDO), 2-methyl-1,3-propanediol (MPO), 2-ethyl-1,3-propanediol (2-E-1,3-PDO), 1,4-pentanediol (1,4-PTD), have not been biologically synthesized before. This work opens up opportunities for synthesizing structurally diverse diols and triols, especially by genome mining, rational design or directed evolution of proper enzymes.