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Review
. 2009 Jun;12(3):252-60.
doi: 10.1016/j.mib.2009.05.002. Epub 2009 May 28.

Chasing the treasures of the sea - bacterial marine natural products

Tobias A M Gulder  1 , Bradley S Moore
Affiliations
Review

Chasing the treasures of the sea - bacterial marine natural products

Tobias A M Gulder et al. Curr Opin Microbiol. 2009 Jun.

Abstract

Bacterial marine natural products are an important source of novel lead structures for drug discovery. The cytotoxic properties of many of these secondary metabolites are of particular interest for the development of new anticancer agents. Tremendous advances in marine molecular biology, genome sequencing, and bioinformatics have paved the way to fully exploit the biomedical potential of marine bacterial products. In addition, unique biosynthetic enzymes discovered from bacteria from the sea have begun to emerge as powerful biocatalysts in medicinal chemistry and total synthesis. The increasingly interdisciplinary field of marine natural product chemistry thus strongly impacts future developments in medicine, chemistry, and biology.

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Figures

Figure 1
Figure 1
Highly bioactive natural products recently isolated from marine cyanobacteria and actinomycetes: largazole (1) from Symploca sp., coibamide (2) from Leptolyngbya sp., somocystinamide A (3) from a Lyngbya majuscula/Schizothrix mixed assemblage, as well as marinopyrroles A (4) and B (5), marineosins A (6) and B (7), and ammosamides A (8) and B (9), all isolated from Streptomyces spp.
Figure 2
Figure 2
Engineered production of eptidemnamide (12) in the heterologous host E. coli by exchanging the ulithiacyclamide (11) sequence (green) in natural PatE2 with the amino acid sequence specifying 12 (yellow). Patellamide C (10, grey) is encoded by both, PatE2 and the recombinant PatEdm.
Figure 3
Figure 3
Proposed biosynthesis of salinosporamide A (13a) and B (13b) involving a novel chlorination pathway initialized by the conversion of 16 to 17 and the generation of a new amino acid building block 14.
Figure 4
Figure 4
Inactivation of key enzymatic processes in salinosporamide biosynthesis, i.e. chlorination (SalL), oxidation (SalD), and precursor amino acid biosynthesis (SalX) in combination with complementary feeding of precursors for the production of novel salinosporamide derivatives with different halogen substituents, oxygenation patterns, and alkyl-substituents, respectively.
Figure 5
Figure 5
Ex vivo total biosynthesis of the bacteriostatic polyketide enterocin (26).
See this image and copyright information in PMC

References

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