An Unexpected Stereochemical Insignificance Discovered in \u3cem\u3eAcinetobacter baumannii\u3c/em\u3e Quorum Sensing

Stereochemistry is a key aspect of molecular recognition for biological systems. As such, receptors and enzymes are often highly stereospecific, only recognizing one stereoisomer of a ligand. Recently, the quorum sensing signaling molecules used by the nosocomial opportunistic pathogen, Acinetobacter baumannii, were identified, and the primary signaling molecule isolated from this species was N-(3-hydroxydodecanoyl)-l-homoserine lactone. A plethora of bacterial species have been demonstrated to utilize 3-hydroxy-acylhomoserine lactone autoinducers, and in virtually all cases, the (R)-stereoisomer was identified as the natural ligand and exhibited greater autoinducer activity than the corresponding (S)-stereoisomer. Using chemical synthesis and biochemical assays, we have uncovered a case of stereochemical insignificance in A. baumannii and provide a unique example where stereochemistry appears nonessential for acylhomoserine lactone-mediated quorum sensing signaling. Based on previously reported phylogenetic studies, we suggest that A. baumannii has evolutionarily adopted this unique, yet promiscuous quorum sensing system to ensure its survival, particularly in the presence of other proteobacteria

Stereochemical Insignificance Discovered in Acinetobacter baumannii Quorum Sensing

Stereochemistry is a key aspect of molecular recognition for biological systems. As such, receptors and enzymes are often highly stereospecific, only recognizing one stereoisomer of a ligand. Recently, the quorum sensing signaling molecules used by the nosocomial opportunistic pathogen, Acinetobacter baumannii, were identified, and the primary signaling molecule isolated from this species was N-(3-hydroxydodecanoyl)-l-homoserine lactone. A plethora of bacterial species have been demonstrated to utilize 3-hydroxy-acylhomoserine lactone autoinducers, and in virtually all cases, the (R)-stereoisomer was identified as the natural ligand and exhibited greater autoinducer activity than the corresponding (S)-stereoisomer. Using chemical synthesis and biochemical assays, we have uncovered a case of stereochemical insignificance in A. baumannii and provide a unique example where stereochemistry appears nonessential for acylhomoserine lactone-mediated quorum sensing signaling. Based on previously reported phylogenetic studies, we suggest that A. baumannii has evolutionarily adopted this unique, yet promiscuous quorum sensing system to ensure its survival, particularly in the presence of other proteobacteria

Utilizing Biocatalysis Toward Asymmetric Pharmaceuticals and Pharmaceutical Intermediates

This presentation was given at Mercer University

Utilizing Engineered E. Coli as An Asymmetric Biocatalyst towards Pharmaceutical Precursors

This presentation was given at SERMACS

Synthesis of Pharmaceutical Precursors Using Biocatalysis

This presentation was given at Florida Gulf Coast University

Biocatalysis: Utilizing Enzymes for the Synthesis of Pharmaceuticals

This presentation was given at the University of Tampa

Utilizing Biocatalysis Toward Asymmetric Pharmaceuticals and Pharmaceutical Intermediates

This presentation was given at Georgia College and State University

Bestatin: Three Decades of Synthetic Strategies

Bestatin (ubenimex) is a dipeptide that can treat a variety of diseases. Over the last thirty years synthetic chemists have developed an assortment of routes to optically pure (-)-Bestatin. Many strategies include the use of pure starting materials like sugars and amino acids. In addition, the utilization of chiral auxiliary groups have been implemented to achieve an increase in stereoselectivity and to simplify the purification process. Lastly, asymmetric catalysis using enzymes or inorganic catalysts has also been used to afford the desired stereochemistry. This review will cover 23 synthetic strategies to (-)-Bestatin through the year 2005

Synthesis of a Natural Product Derivative

This presentation was given at the Armstrong Student Scholarship Symposium

Synthesis of γ-Keto Nitriles and a Biocatalytic Approach to Asymmetric Lactones

This presentation was given at the Armstrong Student Scholarship Symposium