Article
Biochemical Research Methods
Qian Zhang, Shiqin Yu, Yunbin Lyu, Weizhu Zeng, Jingwen Zhou
Summary: This study successfully increased the production of (2S)-naringenin by regulating the fatty acid beta-oxidation pathway and gene expression in yeast, leading to higher levels of acetyl-CoA in the cytosol. Fed-batch fermentation achieved remarkable levels of (2S)-naringenin production, with the highest reported titer in any microorganism.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Microbiology
Jiao Liu, Shanshan Zhang, Wenhao Li, Guanyi Wang, Zhoujie Xie, Wei Cao, Weixia Gao, Hao Liu
Summary: Citric acid is widely used in various industries. This study investigated the roles of cytosolic phosphoketolase (PK), acetate kinase (ACK), and acetyl-CoA synthetase (ACS) in citrate biosynthesis. It was found that PK, ACK, and ACS played important roles in cytosolic acetyl-CoA accumulation and affected citric acid biosynthesis. The study also reconstructed an efficient PK-PTA pathway, which significantly enhanced citric acid production in fermentation.
Article
Biotechnology & Applied Microbiology
Shiyun Li, Wenxuan Fu, Ruifang Su, Yunying Zhao, Yu Deng
Summary: In this study, Saccharomyces cerevisiae was engineered to produce malonate, a valuable chemical compound, through genetic mutations and optimization of the production process. The engineered strain showed significantly increased malonate production.
METABOLIC ENGINEERING
(2022)
Article
Chemistry, Multidisciplinary
Tian Tong, Zhenyan Tao, Xiulai Chen, Cong Gao, Hui Liu, Xiaoling Wang, Gao-Qiang Liu, Liming Liu
Summary: This study established a novel oxaloacetate pathway for efficient 3-HP biosynthesis in yeast through yeast engineering and dephosphorylation regulation strategy, achieving a high-yield production of 3-HP from glucose. It represents a significant advancement in the field of microbial production of platform chemicals.
Review
Endocrinology & Metabolism
Gonzalo Fernandez-Fuente, Michael J. Rigby, Luigi Puglielli
Summary: By regulating intracellular signaling molecules, especially the citrate/acetyl-CoA pathway, homeostatic responses in cells can be activated. The citrate/acetyl-CoA pathway plays important roles in various biological functions within cells and is associated with N epsilon-lysine acetylation. Specifically, in the acetylation machinery of the endoplasmic reticulum (ER), ER acetylation regulates metabolic communication and homeostasis between different cellular organelles, affecting cellular adaptive responses and specific disease states. Therefore, citrate and acetyl-CoA should be recognized as both metabolic substrates and important signaling molecules for cellular adaptation.
MOLECULAR METABOLISM
(2023)
Review
Microbiology
John E. Cronan
Summary: This review provides an update on the research of Escherichia coli acetyl-CoA carboxylase (ACC), focusing on the structures, stoichiometry, regulation of ACC activity and expression.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Han She, Lei Tan, Yuanlin Du, Yuanqun Zhou, Ningke Guo, Jun Zhang, Yunxia Du, Yi Wang, Zhengbin Wu, Chunhua Ma, Qinghui Li, Qingxiang Mao, Yi Hu, Liangming Liu, Tao Li
Summary: In this study, a sepsis model was created using cecal ligation and puncture and lipopolysaccharide. The researchers found that VDAC2 lysine malonylation was elevated in sepsis, and that the malonylation of VDAC2 lysine 46 affected mitochondrial-related ferroptosis and myocardial injury. Malonyl-CoA was identified as the primary inducer of VDAC2 malonylation. Inhibition of malonyl-CoA reduced VDAC2 malonylation and alleviated myocardial dysfunction. Targeting VDAC2 malonylation could be a potential treatment strategy for sepsis-induced myocardial dysfunction.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ryo Mizojiri, Daisuke Tomita, Masako Sasaki, Yoshihiko Satoh, Yukiko Yamamoto, Hiroyuki Sumi, Hironobu Maezaki
Summary: By modifying the molecular length, a new ACC1-selective inhibitor 1i was discovered. Further chemical modification produced compound 1n with potent ACC1 selective inhibition and suitable PK profile for in vivo evaluations. This novel series of potent ACC1-selective inhibitors shows promise as both research tools and potential therapeutic agents.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Albert Fina, Stephanie Heux, Joan Albiol, Pau Ferrer
Summary: This study improves the productivity of Pichia pastoris in producing 3-hydroxypropionic acid by combining different metabolic engineering approaches. The results show that, in combination with using glycerol as a carbon source, the metabolically engineered strains achieved the highest concentration and productivity of 3-hydroxypropionic acid reported so far in yeast.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Food Science & Technology
Wenqi Shi, Jie Li, Yanfang Chen, Yefu Chen, Xuewu Guo, Dongguang Xiao
Summary: Metabolic engineering strategies were utilized to enhance the production of C6-C10 fatty acid ethyl esters in Saccharomyces cerevisiae, including improving precursor accumulation, increasing alcohol acyltransferase activity, and facilitating ester synthesis.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Qian Zhang, Xinglong Wang, Weizhu Zeng, Sha Xu, Dong Li, Shiqin Yu, Jingwen Zhou
Summary: The biosynthetic pathway of carminic acid was reconstructed in Saccharomyces cerevisiae through systematic pathway engineering. The titer of carminic acid reached 7580.9 μg/L in a 5 L bioreactor, the highest reported for a microorganism. Heterologous reconstruction of the carminic acid biosynthetic pathway in S. cerevisiae has great potential for de novo biosynthesis of anthraquinone dye.
METABOLIC ENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Tobias Schwanemann, Maike Otto, Benedikt Wynands, Jan Marienhagen, Nick Wierckx
Summary: In this study, the researchers successfully enhanced the availability of malonyl-CoA in Pseudomonas taiwanensis VLB120, leading to increased production of polyketide compounds. The overexpression of acetyl-CoA carboxylase was found to play a key role in the production of polyketides, and its effectiveness depended on the strain-background and the impairment of downstream fatty acid synthesis.
METABOLIC ENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Xiangxiang Wang, Yuyu Zhao, Zhaohua Hou, Xiaoxu Chen, Shuangying Jiang, Wei Liu, Xin Hu, Junbiao Dai, Guanghou Zhao
Summary: This study presents a framework to rewrite the central metabolic pathway for malonyl-CoA biosynthesis in yeast and assess its output. By introducing genetic mutations into the genes encoding the pathway, millions of enzyme variants were generated and tested, resulting in the identification of beneficial mutants with increased malonyl-CoA production. Furthermore, integrating these mutants generated diverse phenotypes, including higher production of malonyl-CoA and other metabolites.
METABOLIC ENGINEERING
(2023)
Review
Neurosciences
Neeraj Chhimpa, Neha Singh, Nikkita Puri, Hanuman Prasad Kayath
Summary: Citrate synthase is an important enzyme in mitochondria that plays a vital role in energy production. Low levels of citrate synthase in the brains of Alzheimer's disease patients have been shown to result in reduced cellular energy and impairment of cognitive function. However, studies have also demonstrated that citrate can inhibit the aggregation of amyloid-beta, a key factor in the development of Alzheimer's disease.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Review
Immunology
Monica Dominguez, Bernhard Bruene, Dmitry Namgaladze
Summary: Recent studies have shown the profound influence of metabolism on immune responses, particularly through epigenetic regulation of gene expression. ACLY plays a crucial role in the formation of cytosolic acetyl-CoA, supporting de novo lipogenesis and contributing to epigenetic regulation through histone acetylation. Alternative sources of acetyl-CoA also play a role in metabolic and epigenetic regulation in immune cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Antoine H. Chaanine, LeeAnn Higgins, Todd Markowski, Jarrod Harman, Maureen Kachman, Charles Burant, L. Gabriel Navar, David Busija, Patrice Delafontaine
Summary: Metabolic remodeling plays a significant role in the pathophysiology of heart failure, and the crosstalk between PKA and AMPK signaling governs metabolic remodeling in myocardial remodeling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Endocrinology & Metabolism
Mirza Muhammad Fahd Qadir, Weiwei Xu, Daniela Nasteska, Manika Bhondeley, Paula Mota de Sa, Charles R. Evans, Jochen Buck, Lonny Levin, Charles Burant, David Hodson, Franck Mauvais-Jarvis
Article
Biochemistry & Molecular Biology
Carolyn F. McCabe, Jennifer L. LaBarre, Steven E. Domino, Marjorie C. Treadwell, Ana Baylin, Charles F. Burant, Dana C. Dolinoy, Vasantha Padmanabhan, Jaclyn M. Goodrich
Summary: Maternal prenatal status plays a crucial role in offspring health and disease, and alterations in DNA methylation may be a mechanism through which suboptimal prenatal conditions confer disease risk later in life. This study investigated the association between maternal one-carbon metabolites and DNA methylation patterns in newborns. The findings highlight the importance of maternal diet and cellular methylation potential in shaping offspring health.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2022)
Article
Neurosciences
Cheehoon Ahn, Benjamin J. Ryan, Michael W. Schleh, Pallavi Varshney, Alison C. Ludzki, Jenna B. Gillen, Douglas W. Van Pelt, Lisa M. Pitchford, Suzette M. Howton, Thomas Rode, Scott L. Hummel, Charles F. Burant, Jonathan P. Little, Jeffrey F. Horowitz
Summary: Even without weight loss, 12 weeks of exercise training can alter adipose tissue structure and factors that regulate metabolism and the inflammatory signal pathway in adults with obesity.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Endocrinology & Metabolism
Michael J. MacDonald, Israr-ul H. Ansari, Amy S. Riedemann, Scott W. Stoker, Jens C. Eickhoff, Peter J. Chlebeck, Luis A. Fernandez, Melissa J. Longacre
Summary: Net synthesis of pancreatic beta-cells peaks before 2 years of age and beta-cell mass is set within the first 5 years of life. In-frame translational readthrough of the NRP1 gene generates a truncated neuropilin-1 protein, which lacks downstream sequence necessary for binding VEGF and stimulates beta-cell replication. Decreased insulin cells and a genetic marker in NRP1 intron 9 are associated with early onset of type 1 diabetes.
Article
Endocrinology & Metabolism
Mary Ellen Vajravelu, Emily Hirschfeld, Acham Gebremariam, Charles F. Burant, William H. Herman, Karen E. Peterson, Jennifer L. Meijer, Joyce M. Lee
Summary: This study evaluated the prospective test performance of different screening measures for identifying dysglycemia in youth. The results showed that HbA1c and nonfasting glucose tests had reasonable longitudinal discrimination in identifying adolescents at risk for dysglycemia, but their performance depended on the definition of the outcome.
HORMONE RESEARCH IN PAEDIATRICS
(2023)
Article
Endocrinology & Metabolism
Johanna Y. Fleischman, Nathan R. Qi, Mary K. Treutelaar, Steven L. Britton, Lauren G. Koch, Jun Z. Li, Charles F. Burant
Summary: Caloric restriction improves metabolic health and shares similarities with high cardiorespiratory fitness in terms of adiposity reduction, enhanced cardiometabolic health, and increased longevity. This study investigates whether the mechanisms through which heritable high cardiorespiratory fitness occurs are similar to those promoting health and longevity through caloric restriction. The results suggest that caloric restriction has positive effects on physiological parameters in low cardiorespiratory fitness rats that resemble those seen in high cardiorespiratory fitness rats.
MOLECULAR METABOLISM
(2023)
Article
Genetics & Heredity
Muhammad Shoaib, Qiang Ye, Heidi IglayReger, Meng H. H. Tan, Michael Boehnke, Charles F. F. Burant, Scott A. A. Soleimanpour, Sarah A. Gagliano A. Taliun
Summary: Polygenic risk scores (PRS) can quantify the genetic susceptibility to disease by analyzing summary statistics from genome-wide association studies (GWAS). Differentiating between type 1 (T1D) and type 2 (T2D) diabetes accurately is crucial for diagnosis and treatment. PRS have the potential to address misclassification of T1D and T2D.
GENETIC EPIDEMIOLOGY
(2023)
Article
Endocrinology & Metabolism
Michael W. W. Schleh, Benjamin J. J. Ryan, Cheehoon Ahn, Alison C. C. Ludzki, Pallavi Varshney, Jenna B. B. Gillen, Douglas W. W. Van Pelt, Lisa M. M. Pitchford, Suzette M. M. Howton, Thomas Rode, Thomas L. L. Chenevert, Scott L. L. Hummel, Charles F. F. Burant, Jeffrey F. F. Horowitz
Summary: The objective of this study was to assess the relationship between insulin-mediated glucose uptake and clinical outcomes, as well as deep-phenotyping measures. The study also aimed to examine how adipocyte size, fibrosis, and proteomic profile contribute to the regulation of fatty acid rate of appearance.
Article
Cell Biology
Weiwei Xu, M. M. Fahd Qadir, Daniela Nasteska, Paula Mota de Sa, Caroline M. Gorvin, Manuel Blandino-Rosano, Charles R. Evans, Thuong Ho, Evgeniy Potapenko, Rajakrishnan Veluthakal, Fiona B. Ashford, Stavroula Bitsi, Jia Fan, Manika Bhondeley, Kejing Song, Venkata N. Sure, Siva S. V. P. Sakamuri, Lina Schiffer, Wandy Beatty, Rachael Wyatt, Daniel E. Frigo, Xiaowen Liu, Prasad V. Katakam, Wiebke Arlt, Jochen Buck, Lonny R. Levin, Tony Hu, Jay Kolls, Charles F. Burant, Alejandra Tomas, Matthew J. Merrins, Debbie C. Thurmond, Ernesto Bernal-Mizrachi, David J. Hodson, Franck Mauvais-Jarvis
Summary: Male mice without androgen receptor (AR) in pancreatic 0 cells have reduced insulin secretion and develop hyperglycemia. Testosterone activates an extranuclear AR, which enhances glucagon-like peptide-1 (GLP-1) insulin action. This study investigates the mechanisms through which testosterone enhances GLP-1-stimulated insulin secretion in male 0 cells, including the activation of cAMP production and the recruitment of Gas to GLP-1 receptor and AR complexes. Additionally, testosterone promotes insulin secretion in human islets through an actin remodeling cascade. The study provides insights into the genomic and non-genomic actions of AR in regulating insulin exocytosis.
Article
Neurosciences
Jan Krzysztof Blusztajn, Nurgul Aytan, Thekkelnaycke Rajendiran, Tiffany J. Mellott, Tanu Soni, Charles F. Burant, Geidy E. Serrano, Thomas G. Beach, Honghuang Lin, Thor D. Stein
Summary: This study identified monogalactosyl diglycerides (MGDGs) as a central correlate of clinical and pathological progression in Alzheimer's disease (AD). The levels of MGDGs were found to be positively associated with AD-related traits in postmortem brain samples. These findings suggest the importance of MGDG metabolism in the progression of AD.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Endocrinology & Metabolism
Johanna Y. Fleischman, Francoise Van den Bergh, Nicole L. Collins, Madelyn Bowers, Daniel A. Beard, Charles F. Burant
Summary: This study investigates the differences in substrate preference and mitochondrial respiration between high capacity runner (HCR) and low capacity runner (LCR) rat lines. The results show that HCR rats have upregulated mitochondrial gene expression and higher fatty acid oxidative capacity compared to LCR rats. This increased fatty acid oxidation is likely a result of selection for running capacity and contributes to the healthy metabolic phenotype of individuals with high cardiorespiratory fitness.
MOLECULAR METABOLISM
(2023)
Article
Medicine, Research & Experimental
Allison C. Billi, Rachael Wasikowski, Feiyang Ma, Srilakshmi Yalavarthi, Claire K. Hoy, Yu Zuo, Matthew T. Patrick, Neha Shah, Christine Parker, Chad Aaronson, Alyssa Harbaugh, Matthew F. Lucido, Kerby Shedden, Krishna Rao, Heidi B. Iglayreger, Charles F. Burant, J. Michelle Kahlenberg, Lam C. Tsoi, Johann E. Gudjonsson, Jason S. Knight, Yogendra Kanthi
Summary: The risk of severe disease and death from COVID-19 is higher in certain patient demographic groups, such as older individuals, males, and those who are obese. A study found that there are distinct immune cell responses in these higher risk groups, including altered neutrophil maturation in older patients and enhanced cytokine responses in male patients. These findings emphasize the importance of studying diverse patient cohorts in COVID-19 immune therapy research.
Meeting Abstract
Environmental Sciences
Rebekah L. Petroff, Vasantha Padmanabhan, Raymond Cavalcante, Charles Burant, Dana C. Dolinoy, Jaclyn M. Goodrich
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)
Article
Endocrinology & Metabolism
Liujun Chen, Lisha Li, Donghong Cui, Yiheng Huang, Haibin Tong, Haleh Zabihi, Shuxia Wang, Yadan Qi, Ted Lakowski, Lin Leng, Suixin Liu, Hong Wu, Lawrence H. Young, Richard Bucala, Dake Qi
Summary: Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. Cytokine macrophage migration inhibitory factor (MIF) plays a role in regulating adipose HSL and adipocyte hypertrophy. Both intracellular and extracellular MIF have opposing effects on HSL, but extracellular action predominates to downregulate HSL and exacerbate obesity development during high-fat diet (HFD).
MOLECULAR METABOLISM
(2024)
Article
Endocrinology & Metabolism
Mengyang Tang, Yi Zhang, Rong Zhang, Yuemei Zhang, Jiangfei Zheng, Daixi Wang, Xinyu Wang, Jing Yan, Cheng Hu
Summary: This study aimed to explore the role of GPSM1 in POMC neurons and the underlying mechanisms in metabolic homeostasis. Through various molecular, biochemical, immunofluorescent, immunohistochemical analyses, and cell culture studies, the study revealed the pathophysiological role of GPSM1 in POMC neurons and its regulation of POMC neuron activity.
MOLECULAR METABOLISM
(2024)