Catabolite Repression Research Articles

Regulatory dynamics of arginine metabolism in Staphylococcus aureus.

Staphylococcus aureus is a highly significant pathogen with several well studied and defined virulence factors. However, the metabolic pathways that are required to facilitate infection are not well described. Previous data have documented that S. aureus requires glucose catabolism during initial stages of infection. Therefore, certain nutrients whose biosynthetic pathway is under carbon catabolite repression and CcpA, including arginine, must be acquired from the host. However, even though S. aureus encodes pathways to synthesize arginine, biosynthesis of arginine is repressed even in the absence of glucose. Why is S. aureus a functional arginine auxotroph? This review discusses recently described regulatory mechanisms that are linked to repression of arginine biosynthesis using either proline or glutamate as substrates. In addition, recent studies are discussed that shed insight into the ultimate mechanisms linking arginine auxotrophy and infection persistence.

Causal effect of fasting serum glucose on atherosclerotic cardiovascular disease: a multivariable Mendelian randomization

Causal effect of fasting serum glucose on atherosclerotic cardiovascular disease: a multivariable Mendelian randomization

Effects of Sugar in Adult Diet on the Development and Reproduction of Spodoptera frugiperda (J. E. Smith) under Laboratory Conditions in Burkina Faso

The fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is the pest causing enormous economic losses to Maize production. To date, there is little documentation on rearing protocols for S. frugiperda. This study aimed to evaluate the effect of honey and glucose as a nutrient source on the developmental parameters and reproduction of S. frugiperda under laboratory conditions. In this work, we compared the larval period, larval survival, pupal period, pupal survival, adult longevity, female oviposition period, female fecundity and egg hatching of S. frugiperda adults under three feed diets: distilled water (D1), 10% bee honey with water solution (D2) and 10% glucose with water (D3). The longest larval period and highest larval survival were achieved on D3. The longest longevity, oviposition and post-oviposition periods, the highest fecundity and number of eggs per female per day were observed on D3. The diet D3 had significant effects on live cycle of S. frugiperda parameters compared with D1 and D2. Our results will enable us to improve mass rearing of S. frugiperda in laboratory.

Transcellular transport of 18F-deoxyglucose via facilitative glucose channels in experimental peritoneal dialysis.

Local and systemic side effects of glucose remain major limitations of peritoneal dialysis (PD). Glucose transport during PD is thought to occur via inter-endothelial pathways, but recent results show that phloretin, a general blocker of facilitative glucose channels (glucose transporters [GLUTs]), markedly reduced glucose diffusion capacity indicating that some glucose may be transferred via facilitative glucose channels (GLUTs). Whether such transport mainly occurs into (absorption), or across (trans-cellular) peritoneal cells is as yet unresolved. Here we sought to elucidate whether diffusion of radiolabeled 18F-deoxyglucose ([18F]-DG) in the opposite direction (plasma → dialysate) is also affected by GLUT inhibition. During GLUT inhibition, such transport may either be increased or unaltered (favors absorption hypothesis) or decreased (favors transcellular hypothesis). Effects on the transport of solutes other than [18F]-DG (or glucose) during GLUT inhibition indicate effects on paracellular transport (between cells) rather than via GLUTs. GLUT inhibition using phloretin markedly reduced [18F]-DG diffusion capacity, improved ultrafiltration (UF) rates and enhanced the sodium dip. No other solutes were significantly affected with the exception of urea and bicarbonate. The present results indicate that part of glucose is transported via the transcellular route across cells in the peritoneal membrane. Regardless of the channel(s) involved, inhibitors of facilitative GLUTs may be promising agents to improve UF efficacy in patients treated with PD.

Mutagenesis combined with 2-deoxyglucose is not a suitable tool to select strains of Papiliotrema laurentii less sensitive to glucose catabolite repression

Mutagenesis combined with 2-deoxyglucose is not a suitable tool to select strains of Papiliotrema laurentii less sensitive to glucose catabolite repression

ITGB1 Alleviates High Glucose-Induced Myocardial Cell Injury by Inhibiting Endoplasmic Reticulum Stress and Cell Apoptosis.

Diabetic cardiopathy is a common clinical complication of diabetes and is one of the main causes of mortality in type 2 diabetes mellitus patients. In this study, we examined the effect and mechanism of integrin β1 (ITGB1) on high glucose-induced myocardial cell injury. High glucose exposure inhibits the expression of ITGB1 in myocardial cells. ITGB1 inhibited the apoptosis and growth inhibition induced by high glucose. Additionally, the high glucose-induced expression of HSPA5, IRE1α, XBP1, CHOP, ATF6, and cleaved-caspase12 was downregulated significantly when ITGB1 was overexpressed in the presence of high glucose, showing that ITGB1 alleviated endoplasmic reticulum (ER) stress triggered by high glucose. Mechanistically, ITGB1 activated the FAK/ERK singling pathway in high glucose-treated myocardial cells. In the rescue experiment conducted using a signaling pathway inhibitor, overexpression of ITGB1 could not alleviate the effect of high glucose on cell activity and apoptosis in the presence of an inhibitor. In conclusion, ITGB1 alleviates high glucose-induced myocardial cell injury by activating the FAK/ERK singling pathway in myocardial cells. This research contributed to the understanding of the pathogenesis of diabetic cardiopathy and the development of novel drugs and therapeutic targets for it.

12주간 복합운동 수행이 고령여성노인의 SFT, TyG 지수, 대사증후군 위험인자 및 혈관경직도에 미치는 영향

This study investigated the effect of a 12-week combined exercise program senior fitness test, triglyceride-fasting glucose Index, metabolic syndrome risk factors and vascular stiffness in elderly women 75-85 years. The participants were assigned to two groups: CEG, n=16 and a CG, n=16. The combined exercise program was conducted 2 times per week and the session was consist of 60 min for 12 weeks. To test the time interactions between the CEG and the CG, to collected data were analyzed using two-way repeated measures ANOVA. between-group main effecs using ANCOVA. The t-test was used for post-hoc, The level of significance was set at .05. As a result, All of the items of SFT changed positively, and the interation effects in TyG index(p<.001), and the main effects between periods in SBP, DBP(p<.001), interation effects in fasting glucose(p<.05), TG(p<.001), HDL-C(p<.01), and main effects between periods in WC(p<.05) in metabolic syndrome risk factors. In addition, vascular stiffness interactions effect(p<.05). In summary, the combined exercise conducted in this study was found to positive effect on elderly women.

Electrochemical corrosion behavior of α-titanium alloys in simulated biological environments (comparative study).

Titanium (Ti) and its alloys are widely utilized in orthopedic and dental applications due to their favorable mechanical properties and biocompatibility. Notably, titanium exhibits excellent corrosion resistance and can form a stable oxide layer, ensuring the longevity and functionality of implants in challenging physiological environments. This study investigates the corrosion behavior of α-Ti alloy in physiological saline solutions, emphasizing the role of key biomolecules found in the human body, including albumin, glycine, and glucose, as well as additional substances such as hydrogen peroxide (H2O2) and hydroxyapatite (Hap). A comprehensive suite of techniques-namely, open-circuit potential measurements, potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and atomic force microscopy (AFM)-was employed to assess the effects of these biomolecules on corrosion behavior. The findings indicate that, unlike H2O2 and Hap, the biomolecules studied significantly enhance the corrosion resistance of the α-Ti alloy in simulated physiological environments. H2O2, due to its strong oxidative properties, accelerates corrosion, while Hap induces ion release that adversely affects the alloy's stability. The observed improvement in corrosion resistance is attributed to the formation of a stable passive layer on the alloy's surface. Notably, this study presents the first long-term electrochemical and immersion tests conducted at 310 K, elucidating the effects of bovine serum albumin (BSA), H2O2, glycine, glucose, and Hap on the corrosion performance of the α-Ti alloy.

Research progress on the function and regulatory pathways of amino acid permeases in fungi.

Nitrogen sources are pivotal for the formation of fungal mycelia and the biosynthesis of metabolites, playing a crucial role in the growth and development of fungi. Amino acids are integral to protein construction, constitute an essential nitrogen source for fungi. Fungi actively uptake amino acids from their surroundings, a process that necessitates the involvement of amino acid permeases (AAPs) located on the plasma membrane. By sensing the intracellular demand for amino acids and their extracellular availability, fungi activate or suppress relevant pathways to precisely regulate the genes encoding these transporters. This review aims to illustrate the function of fungal AAPs on uptake of amino acids and the effect of AAPs on fungal growth, development and virulence. Additionally, the complex mechanisms to regulate expression of aaps are elucidated in mainly Saccharomyces cerevisiae, including the Ssy1-Ptr3-Ssy5 (SPS) pathway, the Nitrogen Catabolite Repression (NCR) pathway, and the General Amino Acid Control (GAAC) pathway. However, the physiological roles of AAPs and their regulatory mechanisms in other species, particularly pathogenic fungi, merit further exploration. Gaining insights into these aspects could reveal how AAPs facilitate fungal adaptation and survival under diverse stress conditions, shedding light on their potential impact on fungal biology and pathogenicity.

Producing D-Ribose from D-Xylose by Demonstrating a Pentose Izumoring Route.

D-Ribose plays fundamental roles in all living organisms and has been applied in food, cosmetics, health care, and pharmaceutical sectors. At present, D-ribose is predominantly produced by microbial fermentation based on the pentose phosphate pathway (PPP). However, this method suffers from a long synthetic pathway, severe growth defect of the host cell, and carbon catabolite repression (CCR). According to the Izumoring strategy, D-ribose can be produced from D-xylose through only three steps. Being not involved in the growth defect or CCR, this shortcut route is promising to produce D-ribose efficiently. However, this route has never been demonstrated in engineering practice, which hinders its application. In this study, we stepwise demonstrated this route and screened out higher active enzymes for each step. The first D-ribose production from D-xylose through the Izumoring route was achieved. By stepwise enzyme dosage tuning and process optimization, 6.87 g/L D-ribose was produced from 40 g/L D-xylose. Feeding D-xylose further improved the D-ribose titer to 9.55 g/L. Finally, we tested the coproduction of D-ribose and D-allose from corn stalk hydrolysate using the route engineered herein. In conclusion, this study demonstrated a pentose Izumoring route, complemented the engineering practices of the Izumoring strategy, paved the way to produce D-ribose from D-xylose, and provided an approach to comprehensively utilize the lignocellulosic sugars.

The transcription factor FgCreA modulates ergosterol biosynthesis and sensitivity to DMI fungicides by regulating transcription of FgCyp51A and FgErg6A in Fusarium graminearum

Fusarium head blight (FHB), caused by Fusarium graminearum, is a devastating disease that severely affects crop yield and quality worldwide. The catabolite responsive elements A (CreA) plays a critical role in numerous cellular processes in eukaryotes. In this study, we performed a functional characterization of CreA in F. graminearum. Deletion of FgCreA led to the transcriptional upregulation of FgCyp51A and FgErg6A, consequently resulting in elevated levels of ergosterol. This augmented ergosterol content was observed to improve cellular membrane integrity and diminished sensitivity to demethylation inhibitors (DMI) fungicides in F. graminearum. FgCreA is an essential element in carbon catabolite repression (CCR), consequently, the ΔFgcreA mutant was compromised in radial growth on various carbon sources, sexual/asexual development, and deoxynivalenol toxin biosynthesis, which was suppressed due to transcriptional downregulation of the biosynthesis-required enzymes. These results unveil a novel regulatory mechanism of FgCreA, influencing both the pathogenicity of F. graminearum and its sensitivity to DMI fungicides.

The Impact of the Dietary Inflammatory Index, Fasting Blood Glucose, and Smoking Status on the Incidence and Survival of Pancreatic Cancer: A Retrospective Case-Control Study and a Prospective Study.

Pancreatic cancer (PC), a highly malignant cancer with a poor diagnosis, may be influenced by diet-related inflammation. This study examined the association between dietary inflammatory index (DII) scores and the incidence and prognosis of PC in Korea. A total of 55 patients with PC were matched with 280 healthy controls (HCs) by age and sex. We also analyzed the combined effects of DII scores and fasting blood glucose (FBG) levels or smoking status on the risk of PC and performed a survival analysis using the Cox proportional hazards method. The DII scores were higher in the patients with PC than those in HCs (odds ratio [OR] = 3.36, confidence interval [CI] = 1.16-9.73, p = 0.03), and the effect was larger in women (OR = 6.13, CI = 1.11-33.82, p = 0.04). A high DII score was jointly associated with FBG ≥ 126 mg/dL in raising PC risk [OR = 32.5, relative excess risk due to interaction/synergy (RERI/S) index = 24.2/4.34, p-interaction = 0.04], indicating a multiplicative interaction. A high DII score combined with ex/current smoker status increased PC risk through an additive interaction (RERI/S = 1.01/1.54, p-interaction = 0.76). However, DII scores did not influence disease-free survival. The consumption of an anti-inflammatory diet, coupled with maintaining normal FBG levels and abstaining from smoking, may help reduce the risk of PC by mitigating pancreatic inflammation.

Blood glucose and blood pressure lowering effect of diets supplemented with whole unripe plantain flour and effects on altered biomolecules in diabetic/hypertensive rats

Blood glucose and blood pressure lowering effect of diets supplemented with whole unripe plantain flour and effects on altered biomolecules in diabetic/hypertensive rats

Mediating effect of fasting blood glucose and peripheral arterial disease on the relationship between sexual functioning and health-related quality of life among Nigerians with type 2 diabetes

BackgroundPoor glycemic control and sexual dysfunction have been shown to impair health-related quality of life (HRQoL) of individuals with diabetes. However, mediators underlying this relationship have not been evaluated. This study aimed/sought to assess the effect of fasting blood glucose (FBG) and peripheral arterial disease (PAD) on the relationship between sexual functioning (SeF) and HRQoL among Nigerians with type 2 diabetes mellitus (T2DM).MethodsThis cross-sectional study consecutively recruited 210 participants diagnosed with T2DM. The recent FBG and lipid profiles were gleaned from the medical records of the participants. We assessed the ankle-brachial index by 8 MHz handheld vascular Doppler. Participants completed the Changes in Sexual Functioning Questionnaire and Short Form 12 (SF-12) questionnaire to assess SeF and HRQoL, respectively.ResultsSignificant differences exist in HRQoL of participants with good and poor glycemic control (mean rank = 111.02 vs. 93.64, p = 0.035) but none between participants with and without PAD (mean rank = 101.39 vs. 107.60, p = 0.483). There was a significant correlation between SeF and HRQoL (r = 0.181, CI = 0.043–0.313, p = 0.008), and a significant negative correlation between HRQoL and FBG (r = -0.149, CI = -0.284 - -0.008, p = 0.033). There is a significant indirect effect of impact of SeF on HRQoL through FBG (b = -0.027, t = -0.899) and PAD (b = 0.034, t = 1.246). Furthermore, the direct effect of SeF on HRQoL in the presence of the mediators was also significant (b = 0.483, p = 0.001). This shows that PAD and FBG mediates the relationship between SeF and HRQoL.ConclusionGood glycemic control and the absence of PAD mediate the relationship between SeF and HRQoL in Nigerians with T2DM.Clinical trial numberNot applicable.

Assessing the conservation and targets of putative sRNAs in Streptococcus pneumoniae.

RNA regulators are often found in complex regulatory networks and may mediate metabolism and virulence in bacteria. Small RNAs (sRNA's), a class of non-coding RNAs that interact with an mRNA transcript via base pairing, modulate translation initiation and mRNA degradation. To better understand the role of sRNAs in pathogenicity several studies identified sRNAs in Streptococcus pneumoniae , however little functional characterization has followed. The goal of this study is threefold: 1) take an inventory of putative sRNAs in S. pneumoniae ; 2) assess the conservation of these sRNAs; and 3) examine their predicted targets. Three previous studies in S. pneumoniae identified 287 putative sRNAs by high-throughput sequencing using a variety of distinct inclusion criteria. This study narrows the candidates to a list of 59 putative sRNAs. BLAST analysis shows that each of the 59 sequences are highly conserved across the S. pneumoniae pangenome while only 5 sRNAs have corresponding sequences with substantial similarity in other members of the Streptococcus genus. We used four RNA-RNA interaction prediction programs (IntaRNA, CopraRNA, sRNARFTarget, and TargetRNA3) to predict targets for each of the 59 putative sRNAs. Across all probable predictions, only seven sRNAs have overlap in the targets predicted by multiple programs, four of which target numerous transposases. Moreover, sRNAs targeting transposases do so with nearly identical and perfect base pairing. One sRNA, named M63 (Spd_sr37), has several probable targets in the CcpA regulon, a network responsible for global catabolite repression, suggesting a possible biological function in control of carbon metabolism. Further, each M63-target interaction exhibits unique base pairing increasing confidence in the biological relevance of the result. This study produces a curated list of S. pneumoniae putative sRNAs whose predicted targets suggest functional significance in transposon and carbon metabolism regulation.

Abstract 4115947: Empagliflozin Inhibits the Mobilization of CCR2+ Monocyte-Derived Macrophages by Reducing CCL2 Expression in Fibroblasts and Slows the Progression of Heart Failure After Pressure Overload.

Background: The positive effects of sodium glucose co-transporter-2 (SGLT2) inhibitors on reducing cardiovascular mortality and hospitalizations due to heart failure have been well established. Although numerous theories propose explanations for the cardioprotective actions of SGLT2 inhibitors, these hypotheses primarily rely on initial findings and require further validation. Studies have shown that immune cells, particularly macrophages marked by C-C chemokine receptor type 2 (CCR2), contribute to the progression of heart failure by infiltrating the myocardium and inducing detrimental structural changes following myocardial infarction or pressure overload. Purpose: This study aims to investigate whether SGLT2 inhibitors can mitigate heart damage by inhibiting the migration of CCR2+ monocyte-derived macrophages. Methods: In this experiment, male B6 mice were subjected to transverse aortic constriction (TAC) to induce heart failure. Two weeks post-TAC, with heart function confirmed as equal across all groups by echocardiography, one group began receiving daily oral doses of empagliflozin, while another served as the control. At four weeks post-TAC, cardiac function was reassessed. The animals were then euthanized, and their hearts were analyzed using flow cytometry, staining, and qPCR to evaluate heart failure and the involvement of immune cells. Additionally, isolated cardiac fibroblasts were subjected to cyclic stretching to mimic post-TAC mechanical stress. Results: Treatment with empagliflozin resulted in improved cardiac function and reduced congestion in the heart and lungs, indicating alleviation of heart failure. The treatment notably decreased myocardial fibrosis, evident from Picrosirius-red staining and reduced expression of fibrosis-related mRNA. Importantly, empagliflozin specifically reduced the number of CCR2-positive macrophages in the heart, without affecting other types of immune cells. In cardiac fibroblasts that underwent cyclic stretching, empagliflozin pre-treatment diminished the expression of C-C motif chemokine ligand 2 (CCL2), the ligand for CCR2. Conclusion: Empagliflozin’s ability to suppress CCL2 expression in fibroblasts and curtail the recruitment of CCR2+ macrophages may represent a potential strategy to decelerate heart failure progression. These findings advance our understanding of the cardioprotective mechanisms of SGLT2 inhibitors and propose novel therapeutic avenues for heart failure management.

Effect of Protein, Carbohydrate, and Oil on Phytochemical Bioaccessibility and Bioactivities of the Ginkgo biloba L. Leaf Formulations After In Vitro Digestion.

The present work evaluates the effect of casein, glucose, and olive oil on phytochemical bioaccessibility, antioxidant potential (DPPH and FRAP), antidiabetic potential (inhibition of amylase, α-glucosidase, and BSA glycation), and antihyperlipidemic potential (inhibition of lipase) of gingko standardized leaf extract in the form of tablets after in vitro digestion. Gingko extract formulations with protein, carbohydrates, and oil had high (>70%) in vitro bioaccessibility of quercetin, kaempferol, and isorhamnetin after each phases of digestion in comparison to moderate (35-70%) in vitro bioaccessibility from gingko water extract. Formulation with the highest in vitro bioaccessibility of the majority of the tested polyphenolic groups and terpene lactones after oral and intestinal phases was ginkgo with olive oil. High (>70%) antioxidant (DPPH and FRAP), antidiabetic (α-glucosidase and BSA glycation), and antihyperlipidemic potential were detected in almost all ginkgo formulations. Based on the results, we conclude that the in vitro bioaccessibility of individual compounds or groups of compounds depends on whether the tablets are taken with water or with foods (protein, carbohydrates, and oil).

Novel motif associated with carbon catabolite repression in two major Gram-positive pathogen virulence regulatory proteins.

Carbon catabolite repression (CCR) is a widely conserved regulatory process that ensures enzymes and transporters of less-preferred carbohydrates are transcriptionally repressed in the presence of a preferred carbohydrate. This phenomenon can be regulated via a CcpA-dependent or CcpA-independent mechanism. The CcpA-independent mechanism typically requires a transcriptional regulator harboring a phosphotransferase regulatory domain (PRD) that interacts with phosphotransferase system (PTS) components. PRDs contain a conserved histidine residue that is phosphorylated by the PTS-associated HPr-His15~P protein. PRD-containing regulators often harbor additional domains that resemble PTS-associated EIIB protein domains with a conserved cysteine residue that can be phosphorylated by cognate PTS components. We noted that Mga, the PRD-containing central virulence regulator of Streptococcus pyogenes, has an EIIBGat domain containing a cysteine that, based on the presence of a similar motif in glycerol kinase, could be a target for phosphorylation. Using site-directed mutagenesis, we constructed phospho-ablative and phospho-mimetic substitutions of this cysteine and found that these substitutions modify the CCR of the Rgg2/3 quorum-sensing system. Moreover, we provide genetic evidence that the phospho-donor of this cysteine residue is likely to be ManL, the EIIA/B subunit of the mannose PTS system. Interestingly, a structurally distinct virulence gene regulator, PrfA of Listeria monocytogenes, harbors a similar cysteine-containing motif, and phospho-ablative and phospho-mimetic substitutions of the cysteine-altered CCR of PrfA-dependent virulence gene expression. Collectively, our data suggest that phosphorylation of a cysteine within the shared novel motif in Mga and PrfA may be a heretofore missing link between cellular metabolism and virulence.IMPORTANCEIn this study, we identified a novel cysteine-containing motif within the amino acid sequence of two structurally distinct transcriptional regulators of virulence in two Gram-positive pathogens that appears to link carbon metabolism with virulence gene expression. The results also highlight the potential post-translational modification of cysteine in bacterial species, a rare and understudied modification.

The combination of metformin and high glucose increased longevity of Caenorhabditis elegans a DAF-16/FOXO-independent manner: cancer/diabetic model via C. elegans.

Sedentary lifestyles and diets with high glycemic indexes are considered to be contributing factors to the development of obesity, type 2 diabetes in humans. Metformin, a biguanide medication commonly used to treat type 2 diabetes, has been observed to be associated with longevity; however, the molecular mechanisms underlying this observation are still unknown. The effects of metformin and high glucose, which have important roles in aging-related disease such as diabetes and cancer, were studied in lin-35 worms because they are associated with cancer-associated pRb function in mammals and have a tumour suppressor property. According to our results, the negative effect of high glucose on egg production of lin-35 worms was greater than that of N2 worms. High glucose shortened lifespan and increased body length and width in individuals of both strains. Metformin treatment alone extended the lifespan of N2 and lin-35 worms by reducing fertilization efficiency. However, when metformin was administered in the presence of high glucose, the lifespan of lin-35 worms was clearly longer compared to N2 worms. Additionally, we conclude that glucose and metformin in lin35 worms can extend life expectancy through a DAF-16/FOXO-independent mechanism. Furthermore, the results of this study will provide a new perspective on extending mammalian lifespan through the model organism C. elegans.

Transcriptomics-guided rational engineering in Bacillus licheniformis for enhancing poly-γ-glutamic acid biosynthesis using untreated molasses

The utilization of non-food raw materials for microbial synthesis of poly-γ-glutamic acid (γ-PGA) presents a promising alternative to conventional food-based biosynthesis. However, the complex carbon source and composition of molasses, a prevalent non-food raw material, may impose constraints on its conversion and utilization by microorganisms. This study aimed to enhance the capacity of Bacillus licheniformis to convert untreated molasses into γ-PGA through transcriptomic analysis to guide metabolic modifications. Initial results from the transcriptomic analysis indicated that the strain utilizing molasses exhibited decreased expression of genes associated with substrate utilization (Module 1) and by-product synthesis (Module 2), while upregulating genes related to precursor synthesis (Module 3). Furthermore, we performed a knockout of the acetolactate synthase (AlsS) to reduce the synthesis of metabolic by-products and a knockout of the global regulator (CcpA) to alleviate carbon catabolite repression (CCR) and then promote substrate utilization. Ultimately, following the tandem overexpression of precursor supplying key genes, the titer of γ-PGA reached 48.26 g/L with a productivity of 1.15 g/L/h, using untreated molasses as the sole carbon source, which was 3.12-fold of the starting strain. These findings offer significant insights into the cost-effective synthesis of γ-PGA by bioconversion of untreated molasses during fermentation.