A “Second-Generation Process” for the Synthesis ofl-Neopentylglycine:  Asymmetric Reductive Amination Using a Recombinant Whole Cell Catalyst†

2006 ◽  
Vol 10 (3) ◽  
pp. 666-669 ◽  
Author(s):  
Harald Gröger ◽  
Oliver May ◽  
Helge Werner ◽  
Anne Menzel ◽  
Josef Altenbuchner
Keyword(s):  
Second Generation ◽  
Reductive Amination ◽  
Generation Process ◽  
Whole Cell

scholarly journals Collaboration and Composition: Issues for a Second Generation Process Language

1999 ◽  
pp. 75-90 ◽  
Author(s):  
B. C. Warboys ◽  
D. Balasubramaniam ◽  
R. M. Greenwood ◽  
G. N. C. Kirby ◽  
K. Mayes ◽  
...  
Keyword(s):  
Second Generation ◽  
Generation Process

scholarly journals Target Abundance-Based Fitness Screening (TAFiS) Facilitates Rapid Identification of Target-Specific and Physiologically Active Chemical Probes

mSphere ◽  
2017 ◽  
Vol 2 (5) ◽  
Author(s):  
Arielle Butts ◽  
Christian DeJarnette ◽  
Tracy L. Peters ◽  
Josie E. Parker ◽  
Morgan E. Kerns ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Second Generation ◽  
Active Compounds ◽  
Whole Cell ◽  
Competitive Fitness ◽  
Content Type ◽  
Human Fungal Pathogen ◽  
Conventional Drug ◽  
Physiologically Active Compounds

ABSTRACT Conventional drug screening typically employs either target-based or cell-based approaches. The first group rely on biochemical assays to detect modulators of a purified target. However, hits frequently lack drug-like characteristics such as membrane permeability and target specificity. Cell-based screens identify compounds that induce a desired phenotype, but the target is unknown, which severely restricts further development and optimization. To address these issues, we have developed a second-generation target-based whole-cell screening approach that incorporates the principles of both chemical genetics and competitive fitness, which enables the identification of target-specific and physiologically active compounds from a single screen. We have chosen to validate this approach using the important human fungal pathogen Candida albicans with the intention of pursuing novel antifungal targets. However, this approach is broadly applicable and is expected to dramatically reduce the time and resources required to progress from screening hit to lead compound. Traditional approaches to drug discovery are frustratingly inefficient and have several key limitations that severely constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein are constructed, tagged with spectrally distinct fluorescent proteins (FPs), and pooled. The pooled strains are then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture is compared by measuring the intensity of the corresponding FP tags. Chemical-induced population shifts indicate that the bioactivity of a small molecule is dependent upon the target protein’s abundance and thus establish a specific functional interaction. Here, we describe the molecular tools required to apply this technique in the prevalent human fungal pathogen Candida albicans and validate the approach using two well-characterized drug targets—lanosterol demethylase and dihydrofolate reductase. However, our approach, which we have termed target abundance-based fitness screening (TAFiS), should be applicable to a wide array of molecular targets and in essentially any genetically tractable microbe. IMPORTANCE Conventional drug screening typically employs either target-based or cell-based approaches. The first group relies on biochemical assays to detect modulators of a purified target. However, hits frequently lack drug-like characteristics such as membrane permeability and target specificity. Cell-based screens identify compounds that induce a desired phenotype, but the target is unknown, which severely restricts further development and optimization. To address these issues, we have developed a second-generation target-based whole-cell screening approach that incorporates the principles of both chemical genetics and competitive fitness, which enables the identification of target-specific and physiologically active compounds from a single screen. We have chosen to validate this approach using the important human fungal pathogen Candida albicans with the intention of pursuing novel antifungal targets. However, this approach is broadly applicable and is expected to dramatically reduce the time and resources required to progress from screening hit to lead compound.

Research and Development of a Second-Generation Process for Bosentan, an Endothelin Receptor Antagonist

2002 ◽  
Vol 6 (2) ◽  
pp. 120-124 ◽  
Author(s):  
Peter J. Harrington ◽  
Hiralal N. Khatri ◽  
Brad S. DeHoff ◽  
Martin R. Guinn ◽  
Mark A. Boehler ◽  
...  
Keyword(s):  
Research And Development ◽  
Receptor Antagonist ◽  
Second Generation ◽  
Endothelin Receptor Antagonist ◽  
Generation Process ◽  
Endothelin Receptor

scholarly journals Rapid Whole-Cell Assay of Antitubercular Drugs Using Second-Generation Fluoromycobacteriophages

2016 ◽  
Vol 60 (5) ◽  
pp. 3253-3256 ◽  
Author(s):  
Estefanía Urdániz ◽  
Liliana Rondón ◽  
Marcelo A. Martí ◽  
Graham F. Hatfull ◽  
Mariana Piuri
Keyword(s):  
Second Generation ◽  
Whole Cell ◽  
Antitubercular Drugs ◽  
Cell Assay

Second-Generation Process Research Towards Eletriptan: A Fischer Indole Approach

2011 ◽  
Vol 15 (1) ◽  
pp. 98-103 ◽  
Author(s):  
Christopher P. Ashcroft ◽  
Paul Hellier ◽  
Alan Pettman ◽  
Simon Watkinson
Keyword(s):  
Second Generation ◽  
Process Research ◽  
Generation Process

Development of a Second-Generation Process to Antibacterial Candidate Sulopenem

2012 ◽  
Vol 16 (8) ◽  
pp. 1338-1347 ◽  
Author(s):  
Steven J. Brenek ◽  
Stéphane Caron ◽  
Esmort Chisowa ◽  
Roberto Colon-Cruz ◽  
Mark P. Delude ◽  
...  
Keyword(s):  
Second Generation ◽  
Generation Process

scholarly journals Whole cell biotransformation for reductive amination reactions

Bioengineered ◽  
2013 ◽  
Vol 5 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Stephanie Klatte ◽  
Elisabeth Lorenz ◽  
Volker F Wendisch
Keyword(s):  
Reductive Amination ◽  
Whole Cell ◽  
Whole Cell Biotransformation
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