Chemoenzymatic synthesis of an analogue of the potent antifungal mycosubtilin

<p>Mycosubtilin is a naturally occurring antifungal obtained from <em>Bacillus subtilis</em> 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 <em>B. subtilis</em>. 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.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Open Access Thesis

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2013

Author dc:creator

• Srivastava, Mayank

Contributors dc:contributor

• Deborah Heyl-Clegg, Ph.D, Chair
• Jamie Scaglione, Ph.D., Chair
• Hedeel Guy Evans, Ph.D.

• bacillus subtilis
• antibiotics
• molecules
• Organic Chemistry

Repository record dc:identifier

https://commons.emich.edu/theses/492

OAI identifier oai:identifier

oai:commons.emich.edu:theses-1863