UniProt release 15.5
Published July 7, 2009
New insights into drug development with Polyketide synthases
Polyketides are secondary metabolites produced by numerous organisms, from bacteria, fungi and plants to animals. Polyketides are structurally very diverse, thousands of different polyketides have already been discovered, and they possess a wealth of biological activities, including antimicrobial, antifungal and antiparasitic functions. They endow their producing organism with increased fitness in an environment full of competitors. And not only the producers! We also take advantage of these compounds and many are in commercial use as natural insecticides, cholesterol-lowering agents, antitumor drugs or immunosuppressors.
Polyketides are synthesized by an important family of enzymes, called polyketide synthases (PKSs). PKSs are large multifunctional proteins, with an average length of over 2'500 amino acids, up to almost 5'000 amino acids, often bearing several different catalytic activities. Polyketide biosynthesis proceeds by the assembly of simple blocks, such as propionyl-CoA, butyryl-CoA or acetyl-CoA, in a process that closely parallels fatty acid biosynthesis. The fascinating diversity of polyketides arises through various mechanisms: use of different starter molecules, different chain extension substrates, generation of chiral centers, functional group modifications, such as cyclization, etc.
The social amoeba Dictyostelium discoideum lives in the soil and feeds on a variety of bacteria and fungi. In its natural habitat, D. discoideum has several rivals, such as bacteria, nematodes, and Dictyostelium caveatum. However, this slime mold is not defenseless and it has been shown, for instance, to be able to repel nematodes "by secreting compounds". It appears today that D. discoideum has at least 40 functional PKS genes and 5 probable pseudogenes. This is the largest number of PKSs of all known genomes.
These proteins are very interesting. Understanding the exact enzymatic mechanisms in play and the role of each PKS module in the generation of polyketide diversity may allow us to engineer new PKSs that could produce new active compounds. The way may be paved for the discovery of fundamentally new types of drugs!
As of this release, all D. discoideum PKSs can be retrieved from UniProtKB/Swiss-Prot.
Cross-references to UCSC genome browser
Cross-references have been added to the UCSC genome browser, which contains the reference sequences and working draft assemblies for a large collection of genomes and also provides a portal to the ENCODE project.
UCSC is available at http://genome.ucsc.edu/.
The format of the explicit links in the flat file is:
|Resource identifier||UCSC GeneID.|
|Optional information 1||Species name.|
Changes concerning keywords
- Anti-oncogene -> Tumor suppressor