Fatty acid feedstocks enable a highly efficient glyoxylate‐TCA cycle for high‐yield production of β‐alanine

Miao, Yingchun; Liu, Jiao; Wang, Xuanlin; Liu, Bo; Liu, Weifeng; Tao, Yong

doi:10.1002/mlf2.12006

Cited by 8 publications

(3 citation statements)

References 35 publications

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“…These results suggest that 17β-estradiol supplementation can stimulate the CNS and promote BAT thermogenesis, thereby reducing WAT weight. Furthermore, TCA cycle activity is highly correlated with fatty acid absorption and oxidation. , Therefore, an increase in the levels of TCA-cyclic metabolites and fatty acids in the brain suggests active fatty acid absorption and oxidation in the brain through the TCA cycle. Comprehensively, 17β-estradiol supplementation impacts neurotransmitter levels and stimulates the CNS.…”

Section: Results and Discussionmentioning

confidence: 99%

Metabolic Profiling in Plasma and Brain Induced by 17β-Estradiol Supplementation in Ovariectomized Mice

Yang,

Kim,

Yang

et al. 2024

ACS Omega

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17β-Estradiol is an ovarian hormone that regulates energy circulation and storage by acting on the central nervous system. However, the metabolic differences between the blood and brain when stimulated by 17βestradiol are poorly understood. Moreover, research using menopauseinduced models to investigate primary metabolites in the blood and brain is limited. Thus, this study aimed to identify metabolic changes in the plasma and brain resulting from 17β-estradiol supplementation in an estrogendeficient mouse model. Three groups of mice were utilized: sham-operated mice (Sham), ovariectomized mice (OVX), and ovariectomized mice that received a weekly supplementation of 17β-estradiol (E2). Plasma and brain samples from these mice were subjected to metabolic analysis using gas chromatography−time-of-flight−mass spectrometry. Compared with the plasma samples from the Sham and OVX groups, the plasma samples from the E2 group contained higher contents of branched-chain amino acids (BCAAs), such as valine, isoleucine, and leucine. Meanwhile, the brain samples from the E2 group contained higher contents of most metabolites, including BCAAs, neurotransmitters, tricarboxylic acid cycle intermediates, and fatty acids, than those from the two other groups. This study is the first to reveal differences in energy metabolism induced by 17β-estradiol supplementation through brain metabolic profiling of ovariectomized mice, emphasizing the importance of brain metabolic profiling in menopausal hormone research.

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Section: Results and Discussionmentioning

confidence: 99%

Metabolic Profiling in Plasma and Brain Induced by 17β-Estradiol Supplementation in Ovariectomized Mice

Yang,

Kim,

Yang

et al. 2024

ACS Omega

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“…Miao et al (2021) utilized Pichia pastoris for β-alanine production using methanol as a carbon source and obtained 5.60 g/L β-alanine. Miao et al (2022) synthesized β-alanine by modulating the glyoxylate-TCA cycle pathway using fatty acids as raw materials and finally obtained 72.05 g/L β-alanine with a conversion rate as high as 1.24 g/g. This method solved the problems of carbon loss and inhibition of cell growth by using fatty acids as raw materials.…”

Section: Whole-cell Synthesis Of β-Alanine By Microbial Fermentationmentioning

confidence: 99%

Advances in the synthesis of β-alanine

Song,

Zhang,

Wang

et al. 2023

Front. Bioeng. Biotechnol.

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β-Alanine is the only naturally occurring β-type amino acid in nature, and it is also one of the very promising three-carbon platform compounds that can be applied in cosmetics and food additives and as a precursor in the chemical, pharmaceutical and material fields, with very broad market prospects. β-Alanine can be synthesized through chemical and biological methods. The chemical synthesis method is relatively well developed, but the reaction conditions are extreme, requiring high temperature and pressure and strongly acidic and alkaline conditions; moreover, there are many byproducts that require high energy consumption. Biological methods have the advantages of product specificity, mild conditions, and simple processes, making them more promising production methods for β-alanine. This paper provides a systematic review of the chemical and biological synthesis pathways, synthesis mechanisms, key synthetic enzymes and factors influencing β-alanine, with a view to providing a reference for the development of a highly efficient and green production process for β-alanine and its industrialization, as well as providing a basis for further innovations in the synthesis of β-alanine.

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“…Moreover, this biocatalytic method requires expensive precursor and a large amount of enzyme, so many researchers have devoted themselves to developing microbial cell factories through metabolic engineering to produce β-alanine by fermentation [16,17]. A large number of studies have used E. coli as the chassis to improve the biosynthesis of β-alanine [18,19]. Liu et al [20] expressed PanD K104S from B. subtilis, pyruvate carboxylase PC and Asp aminotransferase AspB from C. glutamicum, overexpressed native phosphoenolpyruvate (PEP) carboxylase PPC and L-aspartase AspA, and knocked out pyruvate kinase A (II) gene pykA and D-alanine, D-serine, glycine permease gene cycA in E. coli W3110.…”

Section: Introductionmentioning

confidence: 99%

Multi-strategy combinatorial regulation of β-alanine biosynthesis pathway in Bacillus subtilis

Yang

Rong

et al. 2022

Preprint

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Background β-Alanine is the only naturally occurring β-amino acid and widely used in chemical industry, medicine, food and feed fields. At present, it is more attractive and potential to construct a microbial cell factory through metabolic engineering to produce β-alanine by fermentation. However, the biosynthesis of β-alanine in Bacillus subtilis, a typical industrial model microorganism of food safety grade, has not been thoroughly explored. Results In this study, a total of six L-aspartate-α-decarboxylases (PanDs), including native and two mutant, two other bacterial-derived and one insect-derived, were overexpressed in B. subtilis, respectively. Among them, overexpressions of native PanD and mutant PanDE56S resulted in the greatest increase in β-alanine production, which were 108.14 ± 11.90 mg/L and 104.04 ± 3.11 mg/L after 48 h of fermentation, and 842% and 806% higher than that of the control strain, respectively. Meanwhile, the relative transcription levels of panD were increased by 21.3-fold and 23.9-fold, and the activities of PanD were increased by 43% and 80%. Then, 16 single-gene knockout strains were constructed to block the competing metabolic pathways that consumed phosphoenolpyruvate (PEP), pyruvate, L-glutamate (Glu) and L-aspartate (Asp). Among them, knockouts of ptsG, fbp, ydaP, yhfS, mmgAand pckA, increased β-alanine production by 8.8%, 16.4%, 15.1%, 13.2%, 9.8% and 10.4%, respectively. Subsequently, a multigene knockout strain was constructed that simultaneously knocked out these six genes, resulting in a 40.1% increase in β-alanine production. Furthermore, 10 single-gene suppressor strains were constructed through clustered regularly interspaced short palindromic repeat interference (CRISPRi) technology to inhibit other related competing metabolic pathways, and found that inhibiting the expression of glmS, accB and accA, increased the β-alanine production by 18.4%, 18.1% and 17.7%, respectively. However, the expression of the dCas9 protein resulted in a 13.6% decrease in β-alanine production. Finally, strains expressing endogenous pfkA and aspB, and heterologous ppc were constructed respectively, and found that expression of PEP carboxylase PPC increased the production of β-alanine by 81.7% to 236.15 ± 19.94 mg/L. Conclusions Overexpressions of native PanD and mutant PanDE56S could significantly boost the decarboxylation of Asp to generate β-alanine, which was the key step to limit the excessive synthesis of β-alanine. Genes ptsG, fbp, ydaP, yhfS, mmgA, pckA, and genes glmS, accB, accAwere knockout and repression targets, respectively, that facilitated the β-alanine synthesis. Moreover, introduction of heterologous oxaloacetate anaplerotic reaction mediated by PPC could significantly improve the β-alanine synthesis. In conclusion, this study adopted multiple strategies to investigate the de novo biosynthetic pathway of β-alanine in B. subtilis for the first time, providing a solid foundation for constructing the high-yielding strain of β-alanine in the future.

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Fatty acid feedstocks enable a highly efficient glyoxylate‐TCA cycle for high‐yield production of β‐alanine

Cited by 8 publications

References 35 publications

Metabolic Profiling in Plasma and Brain Induced by 17β-Estradiol Supplementation in Ovariectomized Mice

Metabolic Profiling in Plasma and Brain Induced by 17β-Estradiol Supplementation in Ovariectomized Mice

Advances in the synthesis of β-alanine

Multi-strategy combinatorial regulation of β-alanine biosynthesis pathway in Bacillus subtilis

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