J Chem Inf Model. 2024 Jun 13. doi: 10.1021/acs.jcim.4c00626. Online ahead of print.

ABSTRACT

Venezuelan equine encephalitis virus (VEEV) is a highly virulent pathogen whose nuclear localization signal (NLS) sequence from capsid protein binds to the host importin-α transport protein and blocks nuclear import. We studied the molecular mechanisms by which two small ligands, termed I1 and I2, interfere with the binding of VEEV's NLS peptide to importin-α protein. To this end, we performed all-atom replica exchange molecular dynamics simulations probing the competitive binding of the VEEV coreNLS peptide and I1 or I2 ligand to the importin-α major NLS binding site. As a reference, we used our previous simulations, which examined noncompetitive binding of the coreNLS peptide or the inhibitors to importin-α. We found that both inhibitors completely abrogate the native binding of the coreNLS peptide, forcing it to adopt a manifold of nonnative loosely bound poses within the importin-α major NLS binding site. Both inhibitors primarily destabilize the native coreNLS binding by masking its amino acids rather than competing with it for binding to importin-α. Because I2, in contrast to I1, binds off-site localizing on the edge of the major NLS binding site, it inhibits fewer coreNLS native binding interactions than I1. Structural analysis is supported by computations of the free energies of the coreNLS peptide binding to importin-α with or without competition from the inhibitors. Specifically, both inhibitors reduce the free energy gain from coreNLS binding, with I1 causing significantly larger loss than I2. To test our simulations, we performed AlphaScreen experiments measuring IC50 values for both inhibitors. Consistent with in silico results, the IC50 value for I1 was found to be lower than that for I2. We hypothesize that the inhibitory action of I1 and I2 ligands might be specific to the NLS from VEEV's capsid protein.

PMID:38869471 | DOI:10.1021/acs.jcim.4c00626

Nucleic Acids Res. 2024 Jun 13:gkae481. doi: 10.1093/nar/gkae481. Online ahead of print.

ABSTRACT

Translational research on the Cre/loxP recombination system focuses on enhancing its specificity by modifying Cre/DNA interactions. Despite extensive efforts, the exact mechanisms governing Cre discrimination between substrates remains elusive. Cre recognizes 13 bp inverted repeats, initiating recombination in the 8 bp spacer region. While literature suggests that efficient recombination proceeds between lox sites with non-loxP spacer sequences when both lox sites have matching spacers, experimental validation for this assumption is lacking. To fill this gap, we investigated target site variations of identical pairs of the loxP 8 bp spacer region, screening 6000 unique loxP-like sequences. Approximately 84% of these sites exhibited efficient recombination, affirming the plasticity of spacer sequences for catalysis. However, certain spacers negatively impacted recombination, emphasizing sequence dependence. Directed evolution of Cre on inefficiently recombined spacers not only yielded recombinases with enhanced activity but also mutants with reprogrammed selective activity. Mutations altering spacer specificity were identified, and molecular modelling and dynamics simulations were used to investigate the possible mechanisms behind the specificity switch. Our findings highlight the potential to fine-tune site-specific recombinases for spacer sequence specificity, offering a novel concept to enhance the applied properties of designer-recombinases for genome engineering applications.

PMID:38869070 | DOI:10.1093/nar/gkae481

Int J Hematol Oncol Stem Cell Res. 2024 Apr 1;18(2):110-116. doi: 10.18502/ijhoscr.v18i2.15366.

ABSTRACT

Background: Torque teno virus (TTV) is a globally prevalent virus in humans, yet comprehensive knowledge about its prevalence, predominant transmission routes, and pathogenesis remains limited. This study aimed to assess the frequency of TTV infection among healthy blood donors in Yazd, Iran. Materials and Methods: A total of 236 healthy blood donors, devoid of HIV/HBV/HCV infection markers, participated in the study from 2015 to 2016. Nested Polymerase Chain Reaction (PCR) utilizing a set of oligo primers for the 5΄- UTR region was employed to detect TTV DNA in serum samples. Results: The TTV genome was identified in 161 out of 236 (61.2%) healthy blood donors. The mean age for men and women was 43 and 57 years, respectively. Of the participants, 156 were male, and 107 were female. Donor age exhibited a significant association with virus presence (P=0.007); however, gender did not show a statistically significant association with the frequency of TTV infection in healthy blood donors (P=0.3). Conclusion: The study revealed a notably high frequency of the Torque teno virus in Yazd province, aligning with similar findings globally. Further investigations are warranted to elucidate the clinical implications of the virus in the healthy population.

PMID:38868806 | PMC:PMC11166498 | DOI:10.18502/ijhoscr.v18i2.15366

Imeta. 2022 May 21;1(2):e25. doi: 10.1002/imt2.25. eCollection 2022 Jun.

ABSTRACT

Metaproteomics is a recently thriving technique that studies the collection of proteins in complex microbiomes of the human, animal, plant, and environment. The bioinformatics workflow required for metaproteomics research, from the database search and protein quantification to downstream functional and taxonomic analysis has been challenging and thus limiting the accessibility of metaproteomics to microbiome researchers. To overcome these challenges, we have developed a set of tools named iMetaLab Suite. iMetaLab Suite includes the following components: (1) MetaLab Desktop, an automated database search software that facilities proteins identification and quantitation from microbiomes; (2) the automated iMetaReport that allows users to quickly access database search results and data set profiles; and (3) an interactive online toolset, iMetaShiny, covering most frequently used functional, taxonomic, and statistical analysis in metaproteomics. iMetaLab Suite is a free, easily accessible, and actively updated toolset available to assist researchers to explore metaproteomic data.

PMID:38868572 | PMC:PMC10989937 | DOI:10.1002/imt2.25

Imeta. 2023 Dec 4;3(1):e155. doi: 10.1002/imt2.155. eCollection 2024 Feb.

ABSTRACT

The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at http://www.eyeseeworld.com/cbd.

PMID:38868513 | PMC:PMC10989088 | DOI:10.1002/imt2.155

Imeta. 2023 Aug 17;2(4):e131. doi: 10.1002/imt2.131. eCollection 2023 Nov.

ABSTRACT

The framework of the MicroEXPERT platform. Our Platform was composed of five modules. Data management module: Users upload raw data and metadata to the system using a guided workflow. Data processing module: Uploaded data is processed to generate taxonomical distribution and functional composition results. Metagenome-wide association studies module (MWAS): Various methods, including biomarker analysis, PCA, co-occurrence networks, and sample classification, are employed using metadata. Data search module: Users can query nucleotide sequences to retrieve information in the MicroEXPERT database. Data visualization module: Visualization tools are used to illustrate the metagenome analysis results.

PMID:38868224 | PMC:PMC10989818 | DOI:10.1002/imt2.131

iScience. 2024 Apr 18;27(6):109781. doi: 10.1016/j.isci.2024.109781. eCollection 2024 Jun 21.

ABSTRACT

Sarcomas are a diverse group of rare malignancies composed of multiple different clinical and molecular subtypes. Due to their rarity and heterogeneity, basic, translational, and clinical research in sarcoma has trailed behind that of other cancers. Outcomes for patients remain generally poor due to an incomplete understanding of disease biology and a lack of novel therapies. To address some of the limitations impeding preclinical sarcoma research, we have developed Sarcoma_CellMinerCDB, a publicly available interactive tool that merges publicly available sarcoma cell line data and newly generated omics data to create a comprehensive database of genomic, transcriptomic, methylomic, proteomic, metabolic, and pharmacologic data on 133 annotated sarcoma cell lines. The reproducibility, functionality, biological relevance, and therapeutic applications of Sarcoma_CellMinerCDB described herein are powerful tools to address and generate biological questions and test hypotheses for translational research. Sarcoma_CellMinerCDB (https://discover.nci.nih.gov/SarcomaCellMinerCDB) aims to contribute to advancing the preclinical study of sarcoma.

PMID:38868205 | PMC:PMC11167437 | DOI:10.1016/j.isci.2024.109781

iScience. 2024 May 17;27(6):110010. doi: 10.1016/j.isci.2024.110010. eCollection 2024 Jun 21.

ABSTRACT

Systemic sclerosis (SSc) is a chronic disease characterized by fibrosis and vascular abnormalities in the skin and internal organs, including the lung. SSc-associated pulmonary fibrosis (SSc-PF) is the leading cause of death in SSc patients. Pericytes are key regulators of vascular integrity and endothelial function. The role that pericytes play in SSc-PF remains unclear. We compared the transcriptome of pericytes from SSc-PF lungs (SScL) to pericytes from normal lungs (NORML). We identified 1,179 differentially expressed genes in SScL pericytes. Pathways enriched in SScL pericytes included prostaglandin, PI3K-AKT, calcium, and vascular remodeling signaling. Decreased cyclic AMP production and altered phosphorylation of AKT in response to prostaglandin E2 in SScL pericytes demonstrate the functional consequence of changes in the prostaglandin pathway that may contribute to fibrosis. The transcriptomic signature of SSc lung pericytes suggests that they promote vascular dysfunction and contribute to the loss of protection against lung inflammation and fibrosis.

PMID:38868196 | PMC:PMC11167435 | DOI:10.1016/j.isci.2024.110010

iScience. 2024 May 16;27(6):110011. doi: 10.1016/j.isci.2024.110011. eCollection 2024 Jun 21.

ABSTRACT

Combinatorial signaling by proinflammatory cytokines synergizes to exacerbate toxicity to cells and tissue injury during acute infections. To explore synergism at the gene-regulatory level, we investigated the dynamics of transcription and chromatin signaling in response to dual cytokines by integrating nascent RNA imaging mass spectrometry, RNA sequencing, amplification-independent mRNA quantification, assay for transposase-accessible chromatin using sequencing (ATAC-seq), and transcription factor profiling. Costimulation with interferon-gamma (IFNγ) and tumor necrosis factor alpha (TNFα) synergistically induced a small subset of genes, including the chemokines CXCL9, -10, and -11. Gene induction coincided with increased chromatin accessibility at non-coding regions enriched for p65 and STAT1 binding sites. To discover coactivator dependencies, we conducted a targeted chemogenomic screen of transcriptional inhibitors followed by modeling of inhibitor dose-response curves. These results identified high efficacy of either p300/CREB-binding protein (CBP) or bromodomain and extra-terminal (BET) bromodomain inhibitors to disrupt induction of synergy genes. Combination p300/CBP and BET bromodomain inhibition at half-maximal inhibitory concentrations (subIC50) synergistically abrogated IFNγ/TNFα-induced chemokine gene and protein levels.

PMID:38868181 | PMC:PMC11167439 | DOI:10.1016/j.isci.2024.110011

Heliyon. 2024 May 29;10(11):e32023. doi: 10.1016/j.heliyon.2024.e32023. eCollection 2024 Jun 15.

ABSTRACT

The NLRP3 inflammasome is an intracellular multiprotein complex described to be involved in both an effective host response to infectious agents and various diseases. Investigation into the NLRP3 inflammasome has been extensive in the past two decades, and often revolves around the analysis of a few specific readouts, including ASC-speck formation, caspase-1 cleavage or activation, and cleavage and release of IL-1β and/or IL-18. Quantification of these readouts is commonly undertaken as an endpoint analysis, where the presence of each positive outcome is assessed independently of the others. In this study, we apply time-resolved analysis of a human macrophage model (differentiated THP-1-ASC-GFP cells) to commonly accessible methods. This approach yields the additional quantifiable metrics time-resolved absolute change and acceleration, allowing comparisons between readouts. Using this methodological approach, we reveal (potential) discrepancies between inflammasome-related readouts that otherwise might go undiscovered. The study highlights the importance of time-resolved data in general and may be further extended as well as incorporated into other areas of research.

PMID:38867997 | PMC:PMC11168392 | DOI:10.1016/j.heliyon.2024.e32023

Imeta. 2022 Aug 15;1(4):e47. doi: 10.1002/imt2.47. eCollection 2022 Dec.

ABSTRACT

DNA-based biological ingredient identification and downstream pharmacology network analysis are commonly used in research for Traditional Chinese Medicine preparations (TCM formulas). Advancements in bioinformatics tools and the accumulation of related data have become driving forces for progress in this field. However, a lack of a platform integrating biological ingredient identification and downstream pharmacology network analysis hinders the deep understanding of TCM. In this study, we developed the TCM-Suite platform composed of two sub-databases, Holmes-Suite and Watson-Suite, for TCM biological ingredient identification and network pharmacology investigation, respectively, both are among the most complete: In the Holmes-Suite, we collected and processed six types of marker gene sequences, accounting for 1,251,548 marker gene sequences. In the Watson-Suite, we curated and integrated a massive number of entries from more than 10 public databases. Importantly, we developed a comprehensive pipeline to integrate TCM biological ingredient identification and downstream network pharmacology research, allowing users to simultaneously identify components of a TCM formula and analyze its potential pharmacology mechanism. Furthermore, we designed search engines and a user-friendly platform to better search and visualize these rich resources. TCM-Suite is a comprehensive and holistic platform for TCM-based drug discovery and repurposing. TCM-Suite website: http://TCM-Suite.AImicrobiome.cn.

PMID:38867910 | PMC:PMC10989960 | DOI:10.1002/imt2.47

Imeta. 2022 Mar 6;1(1):e9. doi: 10.1002/imt2.9. eCollection 2022 Mar.

ABSTRACT

It has been proven that three-dimensional protein structures could be modeled by supplementing homologous sequences with metagenome sequences. Even though a large volume of metagenome data is utilized for such purposes, a significant proportion of proteins remain unsolved. In this review, we focus on identifying ecological and evolutionary patterns in metagenome data, decoding the complicated relationships of these patterns with protein structures, and investigating how these patterns can be effectively used to improve protein structure prediction. First, we proposed the metagenome utilization efficiency and marginal effect model to quantify the divergent distribution of homologous sequences for the protein family. Second, we proposed that the targeted approach effectively identifies homologous sequences from specified biomes compared with the untargeted approach's blind search. Finally, we determined the lower bound for metagenome data required for predicting all the protein structures in the Pfam database and showed that the present metagenome data is insufficient for this purpose. In summary, we discovered ecological and evolutionary patterns in the metagenome data that may be used to predict protein structures effectively. The targeted approach is promising in terms of effectively extracting homologous sequences and predicting protein structures using these patterns.

PMID:38867727 | PMC:PMC10989767 | DOI:10.1002/imt2.9

Int J Biol Macromol. 2024 Jun 10:133059. doi: 10.1016/j.ijbiomac.2024.133059. Online ahead of print.

ABSTRACT

Kratom, Mitragyna speciosa, is one of the most popular herbs in the West and Southeast Asia. A number of previous works have focused on bioactive alkaloids in this plant; however, non-alkaloids have never been investigated for their biological activities. Antiviral and virucidal assays of a methanol leaf extract of Kratom, M. speciosa, revealed that a crude extract displayed virucidal activity against the SARS-CoV-2. Activity-guided isolation of a methanol leaf extract of Kratom led to the identification of B-type procyanidin condensed tannins of (-)-epicatechin as virucidal compounds against SARS-CoV-2. The fraction containing condensed tannins exhibited virucidal activity with an EC50 value of 8.38 μg/mL and a selectivity index (SI) value >23.86. LC-MS/MS analysis and MALDI-TOF MS identified the structure of the virucidal compounds in Kratom as B-type procyanidin condensed tannins, while gel permeation chromatograph (GPC) revealed weight average molecular weight of 238,946 Da for high molecular-weight condensed tannins. In addition to alkaloids, (-)-epicatechin was found as a major component in the leaves of M. speciosa, but it did not have virucidal activity. Macromolecules of (-)-epicatechin, i.e., procyanidin condensed tannins, showed potent virucidal activity against SARS-CoV-2, suggesting that the high molecular weights of these polyphenols are important for virucidal activity.

PMID:38866269 | DOI:10.1016/j.ijbiomac.2024.133059

J Steroid Biochem Mol Biol. 2024 Jun 10:106561. doi: 10.1016/j.jsbmb.2024.106561. Online ahead of print.

ABSTRACT

The role of mitochondria in steroidogenesis is well established. However, the specific effects of mitochondrial dysfunction on androgen synthesis are not fully understood. In this study, we investigate the effects of various mitochondrial and metabolic inhibitors in H295R adrenal cells and perform a comprehensive analysis of steroid and metabolite profiling. We report that mitochondrial complex I inhibition by rotenone shifts cells toward anaerobic metabolism with a concomitant hyperandrogenic phenotype characterized by rapid stimulation of dehydroepiandrosterone (DHEA, 2h) and slower accumulation of androstenedione and testosterone (24h). Screening of metabolic inhibitors confirmed DHEA stimulation, which included mitochondrial complex III and mitochondrial pyruvate carrier inhibition. Metabolomic studies revealed truncated tricarboxylic acid cycle with an inverse correlation between citric acid and DHEA production as a common metabolic marker of hyperandrogenic inhibitors. The current study sheds light on a direct interplay between energy metabolism and androgen biosynthesis that could be further explored to identify novel molecular targets for efficient treatment of androgen excess disorders.

PMID:38866189 | DOI:10.1016/j.jsbmb.2024.106561

Sci Total Environ. 2024 Jun 10:173837. doi: 10.1016/j.scitotenv.2024.173837. Online ahead of print.

ABSTRACT

Human activities are having a massive negative impact on biodiversity and ecological processes worldwide. The rate and magnitude of ecological transformations induced by climate change, habitat destruction, overexploitation and pollution are now so substantial that a sixth mass extinction event is currently underway. The biodiversity crisis of the Anthropocene urges scientists to put forward a transformative vision to promote the conservation of biodiversity, and thus indirectly the preservation of ecosystem functions. Here, we identify pressing issues in global change biology research and propose an integrative framework based on multilayer biological networks as a tool to support conservation actions and marine risk assessments in multi-stressor scenarios. Multilayer networks can integrate different levels of environmental and biotic complexity, enabling us to combine information on molecular, physiological and behaviour responses, species interactions and biotic communities. The ultimate aim of this framework is to link human-induced environmental changes to species physiology, fitness, biogeography and ecosystem impacts across vast seascapes and time frames, to help guide solutions to address biodiversity loss and ecological tipping points. Further, we also define our current ability to adopt a widespread use of multilayer networks within ecology, evolution and conservation by providing examples of case-studies. We also assess which approaches are ready to be transferred and which ones require further development before use. We conclude that multilayer biological networks will be crucial to inform (using reliable multi-levels integrative indicators) stakeholders and support their decision-making concerning the sustainable use of resources and marine conservation.

PMID:38866145 | DOI:10.1016/j.scitotenv.2024.173837

Cell. 2024 Jun 7:S0092-8674(24)00533-6. doi: 10.1016/j.cell.2024.05.024. Online ahead of print.

ABSTRACT

Metazoan genomes are copied bidirectionally from thousands of replication origins. Replication initiation entails the assembly and activation of two CMG helicases (Cdc45⋅Mcm2-7⋅GINS) at each origin. This requires several replication firing factors (including TopBP1, RecQL4, and DONSON) whose exact roles are still under debate. How two helicases are correctly assembled and activated at each origin is a long-standing question. By visualizing the recruitment of GINS, Cdc45, TopBP1, RecQL4, and DONSON in real time, we uncovered that replication initiation is surprisingly dynamic. First, TopBP1 transiently binds to the origin and dissociates before the start of DNA synthesis. Second, two Cdc45 are recruited together, even though Cdc45 alone cannot dimerize. Next, two copies of DONSON and two GINS simultaneously arrive at the origin, completing the assembly of two CMG helicases. Finally, RecQL4 is recruited to the CMG⋅DONSON⋅DONSON⋅CMG complex and promotes DONSON dissociation and CMG activation via its ATPase activity.

PMID:38866019 | DOI:10.1016/j.cell.2024.05.024

Cell Syst. 2024 Jun 7:S2405-4712(24)00151-0. doi: 10.1016/j.cels.2024.05.007. Online ahead of print.

ABSTRACT

Transcription factors can promote gene expression through activation domains. Whole-genome screens have systematically mapped activation domains in transcription factors but not in non-transcription factor proteins (e.g., chromatin regulators and coactivators). To fill this knowledge gap, we employed the activation domain predictor PADDLE to analyze the proteomes of Arabidopsis thaliana and Saccharomyces cerevisiae. We screened 18,000 predicted activation domains from >800 non-transcription factor genes in both species, confirming that 89% of candidate proteins contain active fragments. Our work enables the annotation of hundreds of nuclear proteins as putative coactivators, many of which have never been ascribed any function in plants. Analysis of peptide sequence compositions reveals how the distribution of key amino acids dictates activity. Finally, we validated short, "universal" activation domains with comparable performance to state-of-the-art activation domains used for genome engineering. Our approach enables the genome-wide discovery and annotation of activation domains that can function across diverse eukaryotes.

PMID:38866009 | DOI:10.1016/j.cels.2024.05.007

Cell Rep Methods. 2024 Jun 4:100793. doi: 10.1016/j.crmeth.2024.100793. Online ahead of print.

ABSTRACT

Plasma cell-free DNA (cfDNA) fragmentation patterns are emerging directions in cancer liquid biopsy with high translational significance. Conventionally, the cfDNA sequencing reads are aligned to a reference genome to extract their fragmentomic features. In this study, through cfDNA fragmentomics profiling using different reference genomes on the same datasets in parallel, we report systematic biases in such conventional reference-based approaches. The biases in cfDNA fragmentomic features vary among races in a sample-dependent manner and therefore might adversely affect the performances of cancer diagnosis assays across multiple clinical centers. In addition, to circumvent the analytical biases, we develop Freefly, a reference-free approach for cfDNA fragmentomics profiling. Freefly runs ∼60-fold faster than the conventional reference-based approach while generating highly consistent results. Moreover, cfDNA fragmentomic features reported by Freefly can be directly used for cancer diagnosis. Hence, Freefly possesses translational merit toward the rapid and unbiased measurement of cfDNA fragmentomics.

PMID:38866008 | DOI:10.1016/j.crmeth.2024.100793

BMC Genomics. 2024 Jun 12;25(1):594. doi: 10.1186/s12864-024-10456-2.

ABSTRACT

BACKGROUND: Reverse transcription quantitative PCR (RT-qPCR) with intercalating dyes is one of the main techniques to assess gene expression levels used in basic and applied research as well as in diagnostics. However, primer design for RT-qPCR can be complex due to the high demands on primer quality. Primers are best placed on exon junctions, should avoid polymorphic regions, be specific to the target transcripts and also prevent genomic amplification accurately, among others. Current software tools manage to meet all the necessary criteria only insufficiently. Here, we present ExonSurfer, a novel, user-friendly web-tool for qPCR primer design.

RESULTS: ExonSurfer combines the different steps of the primer design process, encompassing target selection, specificity and self-complementarity assessment, and the avoidance of issues arising from polymorphisms. Amplification of potentially contaminating genomic DNA is avoided by designing primers on exon-exon junctions, moreover, a genomic alignment is performed to filter the primers accordingly and inform the user of any predicted interaction. In order to test the whole performance of the application, we designed primer pairs for 26 targets and checked both primer efficiency, amplicon melting temperature and length and confirmed the targeted amplicon by Sanger sequencing. Most of the tested primers accurately and selectively amplified the corresponding targets.

CONCLUSION: ExonSurfer offers a comprehensive end-to-end primer design, guaranteeing transcript-specific amplification. The user interface is intuitive, providing essential specificity and amplicon details. The tool can also be used by command line and the source code is available. Overall, we expect ExonSurfer to facilitate RT-qPCR set-up for researchers in many fields.

PMID:38867172 | DOI:10.1186/s12864-024-10456-2

World J Microbiol Biotechnol. 2024 Jun 13;40(8):240. doi: 10.1007/s11274-024-04043-6.

ABSTRACT

Erythritol, as a new type of natural sweetener, has been widely used in food, medical, cosmetics, pharmaceutical and other fields due to its unique physical and chemical properties and physiological functions. In recent years, with the continuous development of strategies such as synthetic biology, metabolic engineering, omics-based systems biology and high-throughput screening technology, people's understanding of the erythritol biosynthesis pathway has gradually deepened, and microbial cell factories with independent modification capabilities have been successfully constructed. In this review, the cheap feedstocks for erythritol synthesis are introduced in detail, the environmental factors affecting the synthesis of erythritol and its regulatory mechanism are described, and the tools and strategies of metabolic engineering involved in erythritol synthesis are summarized. In addition, the study of erythritol derivatives is helpful in expanding its application field. Finally, the challenges that hinder the effective production of erythritol are discussed, which lay a foundation for the green, efficient and sustainable production of erythritol in the future and breaking through the bottleneck of production.

PMID:38867081 | DOI:10.1007/s11274-024-04043-6