Bioactive Small Molecules Research Articles

Deciphering the bioavailability of dissolved organic matter in thermophilic compost and vermicompost at the molecular level

Studies on compost dissolved organic matter (DOM) previously focus on its composition and humification, without considering DOM bioavailability to understand compost fertility. To decipher the fertility basis of compost, DOM bioavailability in thermophilic compost (TC) and vermicompost (VC) was investigated and linked with its molecular composition. Results showed that DOM bioavailability of VC (36 % BDOC) was generally higher than that of TC (22 % BDOC) due to containing more tannin-like substances. Inversely, only lipid-/carbohydrate-/protein-like substances contributed to DOM bioavailability in TC. Moreover, these differences of bioavailability expanded with C/N decreased in composting materials. Specifically, the %BDOC of VC with N-rich materials (C/N < 25) was 2.1–3.0 times higher than that in TC, while it was only 1.2–1.4 times for C-rich materials (C/N < 25), because N-surplus facilitated the formation of O-/N-containing aromatics (e.g., CHON and tannin) in VC, but inhibited the decomposition of organic materials into small bioactive molecules in TC.

Metagenome-wide analysis uncovers gut microbial signatures and implicates taxon-specific functions in end-stage renal disease

BackgroundThe gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking.ResultsHerein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression.ConclusionThis study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.

An electrochemical sensor based on FeCo bimetallic single-atom nanozyme for sensitive detection of H2O2

Efficient catalytic decomposition of H2O2 is accompanied by electron transfer through Fe-Nx active sites of hemin in the human body. Inspired by this reaction process, the Fe SAs/Co CNs were successfully synthesized by combined Co atomic sites with nitrogen-carbon doped Fe single-atom active sites (SAs). The synergy between transition metals not only reduces agglomeration during synthesis but also improves its own electrical conductivity due to the interaction between Fe and Co that promotes the formation of graphite surface. Crucially, the synergistic effect of the Co site significantly enhanced the peroxidase activity of the Fe SAs and the reaction rate of the Fenton-like reaction, resulting in an efficient detection of H2O2. Catalytic kinetic calculations and enzymatic kinetic calculations were used to verify the electron transfer rate and catalytic performance of their constructed electrochemical sensing interfaces. The results showed that Fe SAs/Co CNs@GCE showed better detection performance than Fe SAs CNs@GCE. It was applied successfully to detect H2O2 released from cells in real-time as well. The linear detection range of Fe SAs/Co CNs@GCE for H2O2 was 1–16664 μM, and the detection limit was as low as 0.25 μM. Furthermore, an electrochemical sensing chip was constructed using Fe SAs/Co CNs@SPE and the prepared microfluidic channel. The constructed portable FeSAs/Co CNs@SPE had a linear range of 1–400 μM and a detection limit of 0.36 μM and achieved the recovery detection of H2O2 in serum. The electrochemical sensing interfaces constructed based on Fe SAs/Co CNs all have efficient catalytic performance and excellent real-time hydrogen peroxide detection performance, which have practical application potential for human oxidative stress level detection. And it provides a novel approach to the trace detection of bioactive small molecules.

In Silico Study of a Small Bioactive Molecule Targeting Topoisomerase II and P53-MDM2 Complex in Triple-Negative Breast Cancer.

Treatment of triple-negative breast cancer (TNBC) is very challenging as only few therapeutic options are available, including chemotherapy. Thus, a constant search for new and effective approaches of therapy that could potentially fight against TNBC and mitigate side effects is "turn-on". Recently, multitarget therapy has come up with huge possibilities, and it may possibly be useful to overcome several concurrent challenges in cancer therapy. Herein, we proposed the inhibition of both Topoisomerase II enzyme and p53-MDM2 (p53 cavity in MDM2) protein complex by the same bioactive molecules for multitarget therapy. RNA-seq analysis was performed to get a network of essential proteins involved in the apoptosis pathway by considering the triple-negative breast cancer cell line (MDA-MB-231). All of the untreated duplicate sample data were retrieved from NCBI (GSC149768). Further, via in silico screening, potent bioactive molecules were screened out to target both Topo II and the p53-MDM2 complex. The results of ligand-based screening involving docking, MMGBSA, ADME/T, MD simulation, and PCA suggested that resveratrol, a plant bioactive molecule, showed more potential binding in the same cavity of target proteins compared with doxorubicin for Topo IIα (5GWK) and etoposide for the second protein target (p53-MDM2 complex; 4OQ3) as the control drug. This is also evident from the in vitro validation in case of triple-negative breast cancer cell lines (MDA-MB-231) and Western blotting analysis. Thus, it paves the scope of multitargeting against triple-negative breast cancer.

Biocatalysis in Drug Design: Engineered Reductive Aminases (RedAms) Are Used to Access Chiral Building Blocks with Multiple Stereocenters.

Novel building blocks are in constant demand during the search for innovative bioactive small molecule therapeutics by enabling the construction of structure-activity-property-toxicology relationships. Complex chiral molecules containing multiple stereocenters are an important component in compound library expansion but can be difficult to access by traditional organic synthesis. Herein, we report a biocatalytic process to access a specific diastereomer of a chiral amine building block used in drug discovery. A reductive aminase (RedAm) was engineered following a structure-guided mutagenesis strategy to produce the desired isomer. The engineered RedAm (IR-09 W204R) was able to generate the (S,S,S)-isomer 3 in 45% conversion and 95% ee from the racemic ketone 2. Subsequent palladium-catalyzed deallylation of 3 yielded the target primary amine 4 in a 73% yield. This engineered biocatalyst was used at preparative scale and represents a potential starting point for further engineering and process development.

A phenotypic screen with Trypanosoma brucei for discovering small molecules that target the SLiM-binding pocket of proliferating cell nuclear antigen orthologs.

Proliferating cell nuclear antigen (PCNA) is a homo-trimeric protein complex that clamps around DNA to tether DNA polymerases to the template during replication and serves as a hub for many other interacting proteins. It regulates DNA metabolic processes and other vital cellar functions through the binding of proteins having short linear motifs (SLiMs) like the PIP-box (PCNA-interacting protein-box) or the APIM (AlkB homolog 2 PCNA-interacting motif) in the hydrophobic pocket where SLiMs bind. However, overproducing TbPCNA or human PCNA (hPCNA) in the pathogenic protist Trypanosoma brucei triggers a dominant-negative phenotype of arrested proliferation. The mechanism for arresting T. brucei proliferation requires the overproduced PCNA orthologs to have functional intact SLiM-binding pocket. Sight-directed mutagenesis studies showed that T. brucei overproducing PCNA variants with disrupted SLiM-binding pockets grew normally. We hypothesized that chemically disrupting the SLiM-binding pocket would restore proliferation in T. brucei, overproducing PCNA orthologs. Testing this hypothesis is the proof-of-concept for a T. brucei-based PCNA screening assay. The assay design is to discover bioactive small molecules that restore proliferation in T. brucei strains that overproduce PCNA orthologs, likely by disrupting interactions in the SLiM-binding pocket. The pilot screen for this assay discovered two hit compounds that linked to predetermined PCNA targets. Compound #1, a known hPCNA inhibitor, had selective bioactivity to hPCNA overproduced in T. brucei, validating the assay. Compound #6 had promiscuous bioactivity for hPCNA and TbPCNA but is the first compound discovered with bioactivity for inhibiting TbPCNA.

Fucosylated dendrimer mediated enhancement of solubility, stability and biological activity of genistein

Phytochemicals derived from plants have been used as traditional medication owing to their potential therapeutic properties and gained recent attention due to their safe toxicological profiles contrary to synthetic drugs. Genistein (GEN) is a phytophenol reported to have an anticancer effect against various cancers including lung cancer, colorectal carcinoma, breast cancer, etc. However, its practical utilization is rendered by its limited aqueous solubility, slow dissolution, low oral bioavailability, poor stability, and non-specific biodistribution. Small bioactive molecules such as sugars are the most facile targeting ligands as almost all types of cancer cells are reported to exhibit the over-expression of sugar receptors in comparison to healthy cells. Sugar-based targeting of tumor sites is often mediated by surface-functionalized dendrimers which can simultaneously improve the efficacy of GEN and enable its site-specific delivery. In the present work, amine-terminated PAMAM dendrimers (DEND) have been used as a delivery carrier for improving the aqueous solubility and efficacy of GEN. Moreover, fucose (FUC) as a small sugar molecule, has been used for tumor-specific functionalization of DEND improving the lung cancer targeting of GEN. FUC conjugation also reduced the amine-terminal associated toxicity of DEND. The encapsulation of GEN in nanoscale FUC-DEND resulted 128 times enhancement in its water solubility, sustained release, improved physicochemical stability, and 22 times enhancement of anticancer activity. The greater cytotoxicity of GEN was attributed to higher cellular uptake and increased apoptosis in A549 human lung cancer cells. Hence, fucose-functionalized dendrimers could be an efficient carrier for the advanced and targeted delivery of phytochemicals.

Modular and Practical 1,2‐Aryl(Alkenyl) Heteroatom Functionalization of Alkenes through Iron/Photoredox Dual Catalysis**

AbstractEfficient methods for synthesizing 1,2‐aryl(alkenyl) heteroatomic cores, encompassing heteroatoms such as nitrogen, oxygen, sulfur, and halogens, are of significant importance in medicinal chemistry and pharmaceutical research. In this study, we present a mild, versatile and practical photoredox/iron dual catalytic system that enables access to highly privileged 1,2‐aryl(alkenyl) heteroatomic pharmacophores with exceptional efficiency and site selectivity. Our approach exhibits an extensive scope, allowing for the direct utilization of a wide range of commodity or commercially available (hetero)arenes as well as activated and unactivated alkenes with diverse functional groups, drug scaffolds, and natural product motifs as substrates. By merging iron catalysis with the photoredox cycle, a vast array of alkene 1,2‐aryl(alkenyl) functionalization products that incorporate a neighboring azido, amino, halo, thiocyano and nitrooxy group were secured. The scalability and ability to rapid synthesize numerous bioactive small molecules from readily available starting materials highlight the utility of this protocol.

Modular and Practical 1,2-Aryl(Alkenyl) Heteroatom Functionalization of Alkenes through Iron/Photoredox Dual Catalysis.

Efficient methods for synthesizing 1,2-aryl(alkenyl) heteroatomic cores, encompassing heteroatoms such as nitrogen, oxygen, sulfur, and halogens, are of significant importance in medicinal chemistry and pharmaceutical research. In this study, we present a mild, versatile and practical photoredox/iron dual catalytic system that enables access to highly privileged 1,2-aryl(alkenyl) heteroatomic pharmacophores with exceptional efficiency and site selectivity. Our approach exhibits an extensive scope, allowing for the direct utilization of a wide range of commodity or commercially available (hetero)arenes as well as activated and unactivated alkenes with diverse functional groups, drug scaffolds, and natural product motifs as substrates. By merging iron catalysis with the photoredox cycle, a vast array of alkene 1,2-aryl(alkenyl) functionalization products that incorporate a neighboring azido, amino, halo, thiocyano and nitrooxy group were secured. The scalability and ability to rapid synthesize numerous bioactive small molecules from readily available starting materials highlight the utility of this protocol.

IDENTIFICATION OF ANTI-ASTHMATIC DRUG FROM MEDICINAL PLANTS USING AN IN SILICO APPROACH

Objectives: Considering the limitations and side effects of current synthetic medications, herein, the exploration of the anti-inflammatory and antihistamine properties of medicinal plants is conducted to provide alternative treatment options for asthma and aims to identify potential anti-asthmatic drugs using an in silico approach. Methods: A molecular docking study was performed to assess the binding affinities and interactions between the neuropeptide S receptor (NPSR) protein and 15 medicinal plants and flavonoids chosen from published literature. A Ramachandran Plot analysis was conducted to evaluate the stereochemical properties of the protein. Furthermore, to gain insights into the drug-likeness and pharmacokinetic properties of the identified ligands, ADMESAR analysis was performed to predict molecular properties and bioactivity of small molecules. Results: Among the 15 medicinal plants investigated in this research, Kaempferol exhibited the least binding energy of −5.05, indicating a highly stable interaction with the NPSR protein. This exceptional stability suggests that Kaempferol has the potential to serve as an effective anti-asthmatic drug. Conclusion: Asthma has no permanent cure, and the current synthetic medications raise long-term safety concerns. This study explored the use of medicinal plants and flavonoids, with Kaempferol showing promise as a potential anti-asthmatic drug candidate. This preliminary study could open avenues to further research and the use of medicinal plants in the treatment of asthma, potentially reducing reliance on synthetic drugs.

CaO2 Nanomedicines: A Review of Their Emerging Roles in Cancer Therapy.

Nanomedicines based on nanoscale metal peroxides have multifunctional properties for cancer theranostics, such as producing bioactive small molecules (e.g., metal ions, H2O2, O2, and OH-). Among various metal peroxides, calcium peroxide (CaO2) nanomedicines are widely studied due to their easy synthesis and biocompatibility. CaO2 nanoparticles can treat cancers through three main mechanisms: (1) producing O2 to alleviate tumor hypoxia and enhance O2-dependent therapies (e.g., chemotherapy, photodynamic therapy, and immunotherapy); (2) generating H2O2, the precursor of ·OH that triggers cancer chemodynamic therapy; and (3) releasing Ca2+ that induces calcium overload and calcification, which impair tumor survival (ion-interference therapy). This review summarizes the recent examples of CaO2 nanoparticle-based cancer therapeutic strategies and discusses the challenges and future directions of CaO2 nanomedicines.&#xD.

Anti-fungal bioactive terpenoids in the bioenergy crop switchgrass (Panicum virgatum) may contribute to ecotype-specific microbiome composition

Plant derived bioactive small molecules have attracted attention of scientists across fundamental and applied scientific disciplines. We seek to understand the influence of these phytochemicals on rhizosphere and root-associated fungi. We hypothesize that – consistent with accumulating evidence that switchgrass genotype impacts microbiome assembly – differential terpenoid accumulation contributes to switchgrass ecotype-specific microbiome composition. An initial in vitro Petri plate-based disc diffusion screen of 18 switchgrass root derived fungal isolates revealed differential responses to upland- and lowland-isolated metabolites. To identify specific fungal growth-modulating metabolites, we tested fractions from root extracts on three ecologically important fungal isolates – Linnemania elongata, Trichoderma sp. and Fusarium sp. Saponins and diterpenoids were identified as the most prominent antifungal metabolites. Finally, analysis of liquid chromatography-purified terpenoids revealed fungal inhibition structure – activity relationships (SAR). Saponin antifungal activity was primarily determined by the number of sugar moieties – saponins glycosylated at a single core position were inhibitory whereas saponins glycosylated at two core positions were inactive. Saponin core hydroxylation and acetylation were also associated with reduced activity. Diterpenoid activity required the presence of an intact furan ring for strong fungal growth inhibition. These results inform future breeding and biotechnology strategies for crop protection with reduced pesticide application.

Non-canonical two-step biosynthesis of anti-oomycete indole alkaloids in Kickxellales

BackgroundFungi are prolific producers of bioactive small molecules of pharmaceutical or agricultural interest. The secondary metabolism of higher fungi (Dikarya) has been well-investigated which led to > 39,000 described compounds. However, natural product researchers scarcely drew attention to early-diverging fungi (Mucoro- and Zoopagomycota) as they are considered to rarely produce secondary metabolites. Indeed, only 15 compounds have as yet been isolated from the entire phylum of the Zoopagomycota.ResultsHere, we showcase eight species of the order Kickxellales (phylum Zoopagomycota) as potent producers of the indole-3-acetic acid (IAA)-derived compounds lindolins A and B. The compounds are produced both under laboratory conditions and in the natural soil habitat suggesting a specialized ecological function. Indeed, lindolin A is a selective agent against plant-pathogenic oomycetes such as Phytophthora sp. Lindolin biosynthesis was reconstituted in vitro and relies on the activity of two enzymes of dissimilar evolutionary origin: Whilst the IAA–CoA ligase LinA has evolved from fungal 4-coumaryl-CoA synthetases, the subsequently acting IAA-CoA:anthranilate N-indole-3-acetyltransferase LinB is a unique enzyme across all kingdoms of life.ConclusionsThis is the first report on bioactive secondary metabolites in the subphylum Kickxellomycotina and the first evidence for a non-clustered, two-step biosynthetic route of secondary metabolites in early-diverging fungi. Thus, the generally accepted “gene cluster hypothesis” for natural products needs to be reconsidered for early diverging fungi.

Native-compound-Coupled Affinity Matrix (NCAM) in target identification and validation of bioactive compounds: Application, mechanism and outlooks

In drug discovery and development, the direct target identification of bioactive small molecules plays a significant role for understanding the mechanism of action, predicting the side effects, and rationally designing more potent compounds. However, due to the complicated regulatory processes in a cell together with thousands of biomacromolecules, target identification is always the major obstacle. New methods and technologies are continuously invented to tackle this problem. Nevertheless, the mainly used tools possess several disadvantages. High synthetic skills are typically required to laboriously synthesize a probe for protein enrichment. To detect the ligand–protein interaction by analyzing proteins’ responses to proteolytic or thermal treatment, costly and precise instruments are always necessary. Therefore, convenient and practical techniques are urgently needed. Over the past decades, a strategy using native compounds without the requirement of chemical modification, also termed Native-compound-Coupled Affinity Matrix (NCAM), is developing continuously. Two practical tactics based on “label-free” compounds have been invented and used, that is Photo-cross-linked Small-molecule Affinity Matrix (PSAM) and Native-compound-Coupled CNBr-activated Beads (NCCB). Presently, we will elucidate the characteristics, coupling mechanism, advantages and disadvantages, and future prospect of NCAM in specific target identification and validation.

Distinguishing Competing Mechanistic Manifolds for C(acyl)-N Functionalization by a Ni/N-Heterocyclic Carbene Catalyst System.

Carboxylic acid derivatives are appealing alternatives to organohalides as cross-coupling electrophiles for fine chemical synthesis due to their prevalence in biomass and bioactive small molecules as well as their ease of preparation and handling. Within this family, carboxamides comprise a versatile electrophile class for nickel-catalyzed coupling with carbon and heteroatom nucleophiles. However, even state-of-the-art C(acyl)-N functionalization and cross-coupling reactions typically require high catalyst loadings and specific substitution patterns. These challenges have proven difficult to overcome, in large part due to limited experimental mechanistic insight. In this work, we describe a detailed mechanistic case study of acylative coupling reactions catalyzed by the commonly employed Ni/SIPr catalyst system (SIPr = 1,3-bis(2,6-di-isopropylphenyl)-4,5-dihydroimidazol-2-ylidine). Stoichiometric organometallic studies, in situ spectroscopic measurements, and crossover experiments demonstrate the accessibility of Ni(0), Ni(I), and Ni(II) resting states. Although in situ precatalyst activation limits reaction efficiency, the low concentrations of active, SIPr-supported Ni(0) select for electrophile-first (closed-shell) over competing nucleophile-first (open-shell) mechanistic manifolds. We anticipate that the experimental insights into the nature and controlling features of these distinct pathways will accelerate rational improvements to cross-coupling methodologies involving pervasive carboxamide substrate motifs.

Efficient electrospray deposition of surfaces smaller than the spray plume

Electrospray deposition (ESD) is a promising technique for depositing micro-/nano-scale droplets and particles with high quality and repeatability. It is particularly attractive for surface coating of costly and delicate biomaterials and bioactive compounds. While high efficiency of ESD has only been successfully demonstrated for spraying surfaces larger than the spray plume, this work extends its utility to smaller surfaces. It is shown that by architecting the local “charge landscape”, ESD coatings of surfaces smaller than plume size can be achieved. Efficiency approaching 100% is demonstrated with multiple model materials, including biocompatible polymers, proteins, and bioactive small molecules, on both flat and microneedle array targets. UV-visible spectroscopy and high-performance liquid chromatography measurements validate the high efficiency and quality of the sprayed material. Here, we show how this process is an efficient and more competitive alternative to other conformal coating mechanisms, such as dip coating or inkjet printing, for micro-engineered applications.

Indolealkylamines in the venom of the scorpion Thorellius intrepidus

Scorpions are a group of arthropods that strike fear in many people due to their severe medical symptoms, even death, caused by their venomous stings. Even so, not all scorpion species contain harmful venoms against humans but still have valuable bioactive molecules, which could be used in developing new pharmaceutical leads for treating important diseases. This work conducted a comprehensive analysis of the venom from the scorpion Thorellius intrepidus. The venom of T. intrepidus was separated by size exclusion chromatography, and four main fractions were obtained. Fraction IV (FIV) contained small molecules representing over 90% of the total absorbance at 280 nm. Analysis of fraction FIV by RP-HPLC indicated the presence of three main molecules (FIV.1, FIV.2, and FIV.3) with similar UV absorbance spectra profiles. The molecular masses of FIV.1, FIV.2, and FIV.3 were determined, resulting in 175.99, 190.07, and 218.16 Da, respectively. Further confirmation through 1H-NMR and 13C-NMR analyses revealed that these molecules were serotonin, N-methylserotonin, and bufotenidine. These intriguing compounds are speculated to play a pivotal role in self-defense and increasing venom toxicity and could also offer promising biotechnological applications as small bioactive molecules.

Effect of lawsone-preconditioned mesenchymal stem cells on the regeneration of pancreatic β cells in Type 1 diabetic rats.

Diabetes is one of the major health issues globally. Type 1 diabetes mellitus develops due to the destruction of pancreatic β cells. Mesenchymal stem cells (MSCs) having remarkable self-renewal and differentiation potential, can regenerate β cells. MSCs preconditioned with bioactive small molecules possess enhanced biological features and therapeutic potential under in vivo environment. Interestingly, compounds of naphthoquinone class possess antidiabetic and anti-inflammatory properties, and can be explored as potential candidates for preconditioning MSCs. This study analyzed the effect of lawsone-preconditioned human umbilical cord MSCs (hUMSCs) on the regeneration of β cells in the streptozotocin (STZ)-induced Type 1 diabetes (T1D) rats. hUMSCs were isolated and characterized for the presence of surface markers. MSCs were preconditioned with optimized concentration of lawsone. T1D rat model was established by injecting 50 mg/kg of STZ intraperitoneally. Untreated and lawsone-preconditioned hUMSCs were transplanted into the diabetic rats via tail vein. Fasting blood sugar and body weight were monitored regularly for 4 weeks. Pancreas was harvested and β cell regeneration was evaluated by hematoxylin and eosin staining, and gene expression analysis. Immunohistochemistry was also done to assess the insulin expression. Lawsone-preconditioned hUMSCs showed better anti-hyperglycemic effect in comparison with untreated hUMSCs. Histological analysis presented the regeneration of islets of Langerhans with upregulated expression of βcell genes and reduced expression of inflammatory markers. Immunohistochemistry revealed strong insulin expression in the preconditioned hUMSCs compared with the untreated hUMSCs. It is concluded from the present study that lawsone-preconditioned hMSCs were able to exhibit pronounced anti-hyperglycemic effect in vivo compared with hUMSCs alone.

A controllable self-localized imaging strategy capable of synchronous in situ tracking of local changes in intracellular bioactive small-molecules

A controllable self-localized imaging strategy capable of synchronous in situ tracking of local changes in intracellular bioactive small-molecules

Fermentation improves flavors, bioactive substances, and antioxidant capacity of Bian-Que Triple-Bean Soup by lactic acid bacteria.

The ancient traditional Chinese drink Bian-Que Triple-Bean Soup made by fermentation (FTBS) of Lactococcus lactis subsp. lactis YM313 and Lacticaseibacillus casei YQ336 is a potential functional drink. The effect of fermentation on the flavor and biological activity of FTBS was evaluated by analyzing its chemical composition. Five volatile flavors were detected in modified FTBS. Fermentation decreased the proportion of nonanal (beany flavor substances) but significantly increased the total flavone contents, phenol contents and many bioactive small molecule substances in FTBS. The changes of these substances led to the significant improvement of FTBS sensory evaluation, antioxidant activity and prebiotic potential. This research provides a theoretical basis for the application of Lactic acid bacteria (LAB) in the fermentation of edible plant-based foods and transformation from traditional food to industrial production.