Biosynthetic origin of natural products isolated from marine microorganism–invertebrate assemblages

*Scripps Institution of Oceanography,
Departments of ^†Chemistry and Biochemistry,
^§Pharmacology, and
^‡Biology, and
^¶Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093

Edited by Jerrold Meinwald, Cornell University, Ithaca, NY, and approved December 10, 2007 (received for review October 16, 2007)

Abstract

In all probability, natural selection began as ancient marine microorganisms were required to compete for limited resources. These pressures resulted in the evolution of diverse genetically encoded small molecules with a variety of ecological and metabolic roles. Remarkably, many of these same biologically active molecules have potential utility in modern medicine and biomedical research. The most promising of these natural products often derive from organisms richly populated by associated microorganisms (e.g., marine sponges and ascidians), and often there is great uncertainty about which organism in these assemblages is making these intriguing metabolites. To use the molecular machinery responsible for the biosynthesis of potential drug-lead natural products, new tools must be applied to delineate their genetic and enzymatic origins. The aim of this perspective is to highlight both traditional and emerging techniques for the localization of metabolic pathways within complex marine environments. Examples are given from the literature as well as recent proof-of-concept experiments from the authors' laboratories.

Footnotes

^‖To whom correspondence may be addressed. E-mail: pdorrest{at}ucsd.edu or wgerwick{at}ucsd.edu
Author contributions: T.L.S., P.C.D., and W.H.G. designed research; T.L.S., R.C.C., B.R.C., N.E., D.G., E.E., and P.C.D. performed research; T.L.S., R.C.C., B.R.C., N.E., E.E., P.C.D., and W.H.G. analyzed data; and T.L.S., R.C.C., P.C.D., and W.H.G. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0709851105/DC1.