Marine Peptide Secondary Metabolites

Abstract

A large pro port ion of the marine natural produc ts actu ally u n der clinical inve stigat ion are pept ide sec ondary metabolites with unusual amino acids re sidues. This growing f amily of compounds can be produced via tw o major p athw ays, r ibosomal and nonribosomal. In this c hapt er a re p re sent ed a nd illu strated, with a fe w f amou s examples, ribosomal-and n onribosomal-d erived pe ptides. Atte ntion is focused on fi ve families of biological ly a ctive marine p eptides of d iverse origin, ranging from the old est living ce ll of the world, the cyanobact eria, to more sophisticat ed organisms s uch a s tu nicates or mol lusk s. T he discu ssed pe ptides illu strate d iff erently th e s tructural fe atu re s and diversity f ound in mari ne-derived peptid es; laxaphycins as an example o f true pept ide s; dolast atins, didemnins and kahalalides are discuss ed in connectio n wit h their cl inical trials; a nd azole/azoli ne-c ontaining cyanobactins to exe m plif y the extra ord ina ry c hemi cal dive rs it y wit hin a single organism. Information abou t their biol ogical properties and mec hanisms of a ctio n is disc uss ed when available .

Isolation and Synthesis of Laxaphycin B-Type Peptides: A Case Study and Clues to Their Biosynthesis

“…Laxaphycins are cyclic lipopeptides synthesized through a hybrid PKS/NRPS biosynthetic pathway by different marine or freshwater cyanobacteria. They contain amino acids of alternate stereochemistry ( l or d ) and feature a rare fatty β-amino acid with a linear chain of up to 12 carbons [ 7 ]. Several studies have reported structural variants and likely biosynthetic derivatives of laxaphycins that can be separated into two groups, the laxaphycin A-type peptides, whichare cyclic undecapeptides, and the laxaphycin B-type peptides, which are cyclic dodecapeptides.…”

Thirtieth Anniversary of the Discovery of Laxaphycins. Intriguing Peptides Keeping a Part of Their Mystery

“…The figure suggests a Ser in position 2, a Hyp in position 4, a Hse in position 5, and a d -Tyr in position 6 while the text indicates a Hse, Pro, Ser, and d -Tyr in these respective positions. These slight differences in position and stereochemistry show the complexity that chemists face in confirming structures of natural products [ 9 ].…”

“…Dehydroamino acids are commonly found in cyanobacterial peptides [ 9 ] and more generally in peptides of microbial origin [ 70 ]. Several studies have shown that these amino acids can structure peptides, similarly to 2-aminoisobutyric acid (Aib) [ 71 , 72 ].…”

“…It is therefore highly probable that the associated cyanobacteria synthesize them in order to protect themselves from herbivores, competitors, or fouling organisms. However, the ecological role of laxaphycins remains unclear [ 9 ]. Laxaphycin A, hormothamin A, and lyngbyacyclamides are non-toxic on brine shrimp Artemia , while laxaphycin B is lethal [ 28 , 29 , 39 ].…”

Biological Activities of Cyclic and Acyclic B-Type Laxaphycins in SH-SY5Y Human Neuroblastoma Cells

“…Therefore, these peptides have been selected by evolution in both freshwater and oceanic cyanobacteria and may confer to them an ecological advantage. Laxaphycins are divided in two sub-families: laxaphycin A-type, undecapeptides with a segregation of hydrophobic and hydrophilic residues; and laxaphycin B-type, dodecapeptides in which hydrophobic and hydrophilic residues are alternated [ 8 ]. Laxaphycin B-type members such as laxaphycins B, B2 and B3 have presented antifungal, antimicrobial and cytotoxic activities [ 9 , 10 , 11 , 12 ].…”