Open Access Thesis
Master of Science (MS)
Deborah Heyl-Clegg, Ph.D, Chair
Jamie Scaglione, Ph.D., Chair
Hedeel Guy Evans, Ph.D.
Mycosubtilin is a naturally occurring antifungal obtained from Bacillus subtilis that also displays limited antibiotic activity. Structurally, mycosubtilin is a macrocycliclipoheptapeptide of sequence Asn-Tyr-Asn-Gln-Pro-Ser-Asn, with the N-terminal Asn joined by a β-amino fatty acid. Besides the antifungal and antibiotic activities,these molecules are also hemolytic in nature. Hence, the purpose of this study is to synthesize a potent antifungal analogue of mycosubtilin, with a modified β-amino fatty acid, devoid of any hemolytic activity. A chemoenzymatic approach was used to synthesize the cyclic peptide, which involved the synthesis of the linear peptide chain of desired amino acid sequence, thiophenylderivatization of the peptide at the C-terminus, followed by its enzymatic cyclization using the isolated thioesterase from B. subtilis. Thus far, we have successfully synthesized the analogue of mycosubtilin. Future work will focus on purifying the product and testing it for antifungal and hemolytic activity.
Srivastava, Mayank, "Chemoenzymatic synthesis of an analogue of the potent antifungal mycosubtilin" (2013). Master's Theses and Doctoral Dissertations. 492.