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Biology
Hudson W. Coates, Isabelle M. Capell-Hattam, Ellen M. Olzomer, Ximing Du, Rhonda Farrell, Hongyuan Yang, Frances L. Byrne, Andrew J. Brown
Summary: Cholesterol synthesis is an energy- and oxygen-intensive process, but the regulatory effects of hypoxia on pathway enzymes are not well understood. Researchers have discovered that hypoxia triggers the truncation of the rate-limiting enzyme squalene monooxygenase (SM), allowing it to maintain activity and pathway flux. This mechanism involves increased proteasomal degradation of SM and accumulation of its substrate squalene. These findings provide insights into how SM accommodates fluctuating substrate levels and may contribute to its oncogenic properties.
Article
Chemistry, Multidisciplinary
Tsvetan Kardashliev, Sven Panke, Martin Held
Summary: In this study, a novel one-pot biocatalytic process was demonstrated using recombinant microbial whole cells as catalysts to prepare a versatile chemical intermediate 2,6-bis(hydroxymethyl)pyridine from naturally-occurring 2,6-lutidine. After scale up, bioconversion achieved titers exceeding 12 g L-1 with a space-time yield of 0.8 g L-1 h(-1), offering a simpler and more sustainable alternative to multistep organic synthesis protocols.
Article
Biotechnology & Applied Microbiology
Chansik Yoon, Kyoung Eun Baek, Dongil Kim, Gyun Min Lee
Summary: This article investigates the challenge of achieving high-level expression of recombinant proteins in mammalian cells. The authors propose a method of introducing constitutively active transcription factors to overcome transcriptional limitations, which successfully increases the production of therapeutic proteins.
METABOLIC ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Tao Long, Erik W. Debler, Xiaochun Li
Summary: Cholesterol biosynthesis involves multiple enzymes, and understanding their structures and catalytic mechanisms can provide insights for drug development targeting related diseases.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ji Hee Park, Seung Yeon Jeong, Jun Hee Choi, Eun Hui Lee
Summary: STIM1-R304Q plays a crucial role in human skeletal muscle diseases by inducing hyper-SOCE, disrupting calcium distribution, and causing cellular defects that may lead to deleterious skeletal muscle phenotypes in patients.
Article
Multidisciplinary Sciences
Emily Carroll, Baradwaj Ravi Gopal, Indu Raghavan, Minakshi Mukherjee, Zhen Q. Wang
Summary: Digoxin, a widely prescribed heart medicine, is extracted from the foxglove plant. However, the process by which the plant synthesizes digoxin is largely unknown. In this study, a novel enzyme, P450(scc), involved in digoxin biosynthesis is identified through transcriptomic analysis. This discovery provides new insights into the production of digoxin and related drugs.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Xun Shangguan, Zehua Ma, Minghao Yu, Jie Ding, Wei Xue, Jun Qi
Summary: This study reveals a dependence on SQLE-mediated cholesterol metabolism in castration-resistant prostate cancer with PTEN and p53 deficiency, providing insights for new therapeutic strategies.
Article
Chemistry, Physical
Kristina Schell, Heng Li, Lukas Lauterbach, Kizerbo A. Taizoumbe, Jeroen S. Dickschat, Bernhard Hauer
Summary: This study demonstrates a simple structure-guided strategy to create alternative active site confinement in the squalene-hopene cyclase enzyme. By modifying the substrate tunnel to increase proximity between the substrate and catalytic site, the enzyme's catalytic efficiency was significantly improved.
Article
Biochemistry & Molecular Biology
Galina N. Veremeichik, Dmitry V. Bulgakov, Yuliya A. Konnova, Evgenia V. Brodovskaya, Valeria P. Grigorchuk, Victor P. Bulgakov
Summary: The overexpression of AtCPK1-Ca form increases pathogenesis-related protein levels in Vitis amurensis cell cultures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Peicheng Sun, Zhiyu Huang, Sanchari Banerjee, Marco A. S. Kadowaki, Romy J. Veersma, Silvia Magri, Roelant Hilgers, Sebastian J. Muderspach, Christophe V. F. P. Laurent, Roland Ludwig, David Cannella, Leila Lo Leggio, Willem J. H. van Berkel, Mirjam A. Kabel
Summary: In this study, two new fungal oxidoreductases from the AA16 family were characterized. These enzymes were found to be capable of producing H2O2 by oxidizing low-molecular-weight reductants. The interplay between AA16 proteins and MtLPMO9 proteins significantly enhanced cellulose degradation. These findings provide new insights into the functions of copper-dependent enzymes and the interplay of oxidative enzymes within fungal systems to degrade lignocellulose.
Article
Biochemistry & Molecular Biology
Guang Huan Shen, Joon Hee Hong
Summary: This review discusses the synthesis of five series of 4'-truncated nucleotide phosphonic acid analogues and briefly discusses their biological activity results.
CARBOHYDRATE RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Sharad Sarak, Taresh P. Khobragade, Hyunwoo Jeon, Amol D. Pagar, Pritam Giri, Somin Lee, Hyungdon Yun
Summary: A multienzyme biocatalytic cascade was developed to synthesize nylon monomers with high efficiency and a self-sufficient redox network, utilizing a cell-based modularization strategy to produce 6-aminohexanoic acid and epsilon-caprolactam from cyclohexanol. The designed E. coli consortia showed high yields of the desired products, making it a cost-effective method for nylon precursor production.
Article
Chemistry, Multidisciplinary
Sharad Sarak, Amol D. Pagar, Taresh P. Khobragade, Hyunwoo Jeon, Pritam Giri, Seonga Lim, Mahesh D. Patil, Yechan Kim, Byung-Gee Kim, Hyungdon Yun
Summary: A multienzymatic cascade for the synthesis of 1,6-hexamethylenediamine (HMD) and related alpha,omega-diamines from corresponding cycloalkanols was developed. The biosynthetic pathway was distributed into different modules using an E. coli-based modularization strategy. An engineered transaminase variant was used to drive the reaction towards target product formation, resulting in a high yield of HMD.
Article
Biochemistry & Molecular Biology
Shuang Zhao, Yao Wu, Lei Hu
Summary: The study applied dynamic combinatorial chemistry (DCC) to explore novel cholesterol esterase (CEase) inhibitors, successfully amplifying two substrates (A1H3 and A2H3) from the dynamic combinatorial library (DCL). Compound A1H3 exhibited potent and selective inhibition in in vitro biological evaluation, with over 120 times selectivity for CEase.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Tyler B. Alt, Matthew R. Hoag, Graham R. Moran
Summary: This article presents the first comprehensive kinetic investigation of a bacterial form of DPD, revealing its similarity to the mammalian form in terms of mechanism but with distinct aspects in substrate roles.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Editorial Material
Cell Biology
Ngee Kiat Chua, Hudson W. Coates, Andrew J. Brown
SCIENCE TRANSLATIONAL MEDICINE
(2018)
Editorial Material
Biochemistry & Molecular Biology
Hudson W. Coates, Andrew J. Brown
JOURNAL OF LIPID RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Hudson W. Coates, Ngee Kiat Chua, Andrew J. Brown
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2019)
Article
Biochemistry & Molecular Biology
Nicola A. Scott, Laura J. Sharpe, Isabelle M. Capell-Hattam, Samuel J. Gullo, Winnie Luu, Andrew J. Brown
BIOCHEMICAL JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Isabelle M. Capell-Hattam, Laura J. Sharpe, Lydia Qian, Gene Hart-Smith, Anika V. Prabhu, Andrew J. Brown
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Hiromasa Yoshioka, Hudson W. Coates, Ngee Kiat Chua, Yuichi Hashimoto, Andrew J. Brown, Kenji Ohgane
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Editorial Material
Biochemistry & Molecular Biology
Isabelle M. Capell-Hattam, Andrew J. Brown
Review
Biochemistry & Molecular Biology
Ngee Kiat Chua, Hudson W. Coates, Andrew J. Brown
PROGRESS IN LIPID RESEARCH
(2020)
Review
Biochemistry & Molecular Biology
Laura J. Sharpe, Hudson W. Coates, Andrew J. Brown
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Renhong Yan, Pingping Cao, Wenqi Song, Hongwu Qian, Ximing Du, Hudson W. Coates, Xin Zhao, Yaning Li, Shuai Gao, Xin Gong, Ximing Liu, Jianhua Sui, Jianlin Lei, Hongyuan Yang, Andrew J. Brown, Qiang Zhou, Chuangye Yan, Nieng Yan
Summary: The sterol regulatory element-binding protein (SREBP) pathway is controlled by membrane-embedded sterol sensors Scap, Insig-1 and Insig-2, with 25-hydroxycholesterol (25HC) serving as a master switch. Cryo-electron microscopy analysis revealed the structure of the human Scap and Insig-2 complex in the presence of 25HC, showing the critical role of 25HC binding and Insig association in regulating the pathway.
Article
Biochemistry & Molecular Biology
Isabelle M. Capell-Hattam, Nicole M. Fenton, Hudson W. Coates, Laura J. Sharpe, Andrew J. Brown
Summary: In this study, researchers identified the noncatalytic protein ERG28 as a player in mammalian cholesterol synthesis. They found that ERG28 is transcriptionally regulated by the transcription factor SREBP-2 and interacts with enzymes involved in cholesterol synthesis. Knockout of ERG28 resulted in reduced cholesterol levels and impaired cholesterol synthesis. Additionally, ERG28 knockout also affected the activation of SREBP-2 under sterol-replete conditions. These findings highlight the importance of ERG28 in cholesterol synthesis and suggest that further understanding of this protein could contribute to therapeutic strategies for diseases associated with aberrant cholesterol metabolism.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Biology
Hudson W. Coates, Isabelle M. Capell-Hattam, Ellen M. Olzomer, Ximing Du, Rhonda Farrell, Hongyuan Yang, Frances L. Byrne, Andrew J. Brown
Summary: Cholesterol synthesis is an energy- and oxygen-intensive process, but the regulatory effects of hypoxia on pathway enzymes are not well understood. Researchers have discovered that hypoxia triggers the truncation of the rate-limiting enzyme squalene monooxygenase (SM), allowing it to maintain activity and pathway flux. This mechanism involves increased proteasomal degradation of SM and accumulation of its substrate squalene. These findings provide insights into how SM accommodates fluctuating substrate levels and may contribute to its oncogenic properties.