Biosynthesis of Cyclic Peptides and Depsipeptides in NOSTOC SP ATCC 53789

• Main Author: Becker, Julia E
• Other Authors: Moore, Richard E
• Published: University of Hawaii at Manoa 2009
• Online Access: http://hdl.handle.net/10125/6940

The cyanobacterium Nostoc sp. ATCC53789 produces two interesting families of natural products: the cryptophycins and the nostocyclopeptides. The structures of the cryptophycins, a class of tumor-selective cytotoxins, suggest the involvement of both peptide synthetases and polyketide synthases in their biosynthesis. The nostocyclopeptides are cyclic heptapeptides that feature the unnatural amino acid (2S, 4S)-4-methylproline and an unusual imine linkage between two of the amino acid residues. To identify the biosynthetic gene clusters for these peptides, a cosmid library was generated. Peptide synthetase adenylation domains from Nostoc sp. ATCC53789 were amplified by PCR, using degenerated primers based on core conserved sequences within these domains, and used to screen the library. The library was also screened with a probe derived from nosE, a gene involved in 4-methylproline biosynthesis in Nostoc sp. GSV 224. The nosE probe identified three overlapping cosmids, which when sequenced were found to contain genes consistent with nostocyclopeptide biosynthesis. The putative nostocyclopeptide gene cluster includes two peptide synthetase genes, the second of which terminates in a domain with homology to reductases. The cluster also contains genes that appear to be involved in the biosynthesis of 4-methylproline. === xiii, 49 leaves