Abstract
Azasugar biosynthesis involves a key dehydrogenase that oxidizes 2-amino-2-deoxy-D-mannitol to the 6-oxo compound. The genes encoding homologous NAD-dependent dehydrogenases from Bacillus amyloliquefaciens FZB42, B. atrophaeus 1942, and Paenibacillus polymyxa SC2 were codon-optimized and expressed in BL21(DE3) Escherichia coli. Relative to the two Bacillus enzymes, the enzyme from P. polymyxa proved to have superior catalytic properties with a Vmax of 0.095 ± 0.002 µmol/min/mg, 59-fold higher than the B. amyloliquefaciens enzyme. The preferred substrate is 2- amino-2-deoxy-D-mannitol, though mannitol is accepted as a poor substrate at 3% of the relative rate. Simple amino alcohols were also accepted as substrates at lower rates. Sequence alignment suggested D283 was involved in the enzyme’s specificity for aminopolyols. Point mutant D283N lost its amino specificity, accepting mannitol at 45% the rate observed for 2-amino-2-deoxy-D-mannitol. These results provide the first characterization of this class of zinc-dependent medium chain dehydrogenases that utilize aminopolyol substrates.
Keywords: Aminopolyol, azasugar, biosynthesis, dehydrogenase, mannojirimycin, nojirimycin.
Protein & Peptide Letters
Title:Medium-Chain Dehydrogenases with New Specificity: Amino Mannitol Dehydrogenases on the Azasugar Biosynthetic Pathway
Volume: 21 Issue: 1
Author(s): Yanbin Wu, Jeffrey Arciola and Nicole Horenstein
Affiliation:
Keywords: Aminopolyol, azasugar, biosynthesis, dehydrogenase, mannojirimycin, nojirimycin.
Abstract: Azasugar biosynthesis involves a key dehydrogenase that oxidizes 2-amino-2-deoxy-D-mannitol to the 6-oxo compound. The genes encoding homologous NAD-dependent dehydrogenases from Bacillus amyloliquefaciens FZB42, B. atrophaeus 1942, and Paenibacillus polymyxa SC2 were codon-optimized and expressed in BL21(DE3) Escherichia coli. Relative to the two Bacillus enzymes, the enzyme from P. polymyxa proved to have superior catalytic properties with a Vmax of 0.095 ± 0.002 µmol/min/mg, 59-fold higher than the B. amyloliquefaciens enzyme. The preferred substrate is 2- amino-2-deoxy-D-mannitol, though mannitol is accepted as a poor substrate at 3% of the relative rate. Simple amino alcohols were also accepted as substrates at lower rates. Sequence alignment suggested D283 was involved in the enzyme’s specificity for aminopolyols. Point mutant D283N lost its amino specificity, accepting mannitol at 45% the rate observed for 2-amino-2-deoxy-D-mannitol. These results provide the first characterization of this class of zinc-dependent medium chain dehydrogenases that utilize aminopolyol substrates.
Export Options
About this article
Cite this article as:
Wu Yanbin, Arciola Jeffrey and Horenstein Nicole, Medium-Chain Dehydrogenases with New Specificity: Amino Mannitol Dehydrogenases on the Azasugar Biosynthetic Pathway, Protein & Peptide Letters 2014; 21 (1) . https://dx.doi.org/10.2174/092986652101131219093413
DOI https://dx.doi.org/10.2174/092986652101131219093413 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Therapeutical Approaches of Vasoactive Intestinal Peptide as a Pleiotropic Immunomodulator
Current Pharmaceutical Design Epigenetics and the Environmental Regulation of the Brain's Genome and its Function
Current Psychiatry Reviews Meet Our Editorial Board Member
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Assessing Drug Transport Across the Human Placental Barrier: From In Vivo and In Vitro Measurements to the Ex Vivo Perfusion Method and In silico Techniques
Current Pharmaceutical Biotechnology Hypovitaminosis D is Associated with Endothelial Dysfunction in Patients with Metabolic Syndrome
Current Vascular Pharmacology Impact of Mitochondrial Toxicity of HIV-1 Antiretroviral Drugs on Lipodystrophy and Metabolic Dysregulation
Current Pharmaceutical Design Hyperglycemic Hyperosmolar State Associated with Low-Dose Quetiapine Treatment in a Patient with Bipolar Disorder
Current Drug Safety Pathophysiology of Platelet Resistance to Anti-Aggregating Agents in Insulin Resistance and Type 2 Diabetes: Implications for Anti-Aggregating Therapy
Cardiovascular & Hematological Agents in Medicinal Chemistry 2-Mercapto Benzothiazole Derivatives: As Potential Leads for the Diabetic Management
Medicinal Chemistry Ganoderma lucidum: A Potent Pharmacological Macrofungus
Current Pharmaceutical Biotechnology Insulin Resistance as a Therapeutic Target for Improved Endothelial Function:Metformin
Current Drug Targets - Cardiovascular & Hematological Disorders From Endothelial to β Cells: Insights into Pancreatic Islet Microendothelium
Current Diabetes Reviews The Future of Angiotensin II Inhibition in Cardiovascular Medicine
Current Drug Targets - Cardiovascular & Hematological Disorders Carotenoids and Cardiovascular Risk
Current Pharmaceutical Design Challenges and Perspectives of Antiplatelet Therapy in Patients with Diabetes Mellitus and Coronary Artery Disease
Current Pharmaceutical Design Inhibitors of Apoptosis Proteins (IAPs) as Potential Molecular Targets for Therapy of Hematological Malignancies
Current Molecular Medicine Thyroid Hormones and their Metabolites: Biological Roles and Association with Non-Alcoholic Fatty Liver Disease
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Sodium-glucose Cotransporter 2 Inhibitors: Impact on Body Weight and Blood Pressure Compared with other Antidiabetic Drugs
Cardiovascular & Hematological Disorders-Drug Targets Antifungal Therapy Used in Central Nervous System Fungal Infections
Central Nervous System Agents in Medicinal Chemistry Cell Adhesion Molecules and Cadmium
Current Chemical Biology