Utilizing the power of microbial genetics to bridge the gap between the promise and the application of marine natural products.
Marine organisms are a rich source of secondary metabolites. They have yielded thousands of compounds with a broad range of biomedical applications. Thus far, samples required for preclinical and clinical studies have been obtained by collection from the wild, by mariculture, and by total chemical synthesis. However, for a number of complex marine metabolites, none of these options is feasible for either economic or environmental reasons. In order to proceed with the development of many of these promising therapeutic compounds, a reliable and renewable source must be found. Over the last twenty years, the study of microbial secondary metabolites has greatly advanced our understanding of how nature utilizes simple starting materials to yield complex small molecules. Much of this work has focused on polyketides and nonribosomal peptides, two classes of molecules that are prevalent in marine micro- and macroorganisms. The lessons learned from the study of terrestrial metabolite biosynthesis are now being applied to the marine world. As techniques for cloning and heterologous expression of biosynthetic pathways continue to improve, they may provide our greatest hope for bridging the gap between the promise and application of many marine natural products.
Fortman
J L
JL
Department of Medicinal Chemistry, Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
Sherman
David H
DH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D005827:Genetics, Microbial; D023281:Genomics; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology*; D008386:Marine Biology; D046908:Peptide Biosynthesis, Nucleic Acid-Independent / Q000502:physiology*
D000970:Antineoplastic Agents; D001688:Biological Products; D018942:Macrolides