Secrets of the sea: genes encoding anticancer drug found

The tissues of many marine invertebrates such as sponges, tunicates and other filter feeders contain microbial populations that produce a wide variety of biologically active compounds, some of which have been developed into clinically useful drugs.

The anticancer drug didemnin B, the first marine drug to be clinically tested on humans, was discovered in the Caribbean colonial tunicate Trididemnum solidum over 30 years ago.

An international team involving scientists from the King Abdullah University of Science and Technology (KAUST), Saudi Arabia, now reports in the Journal of the American Chemical Society that didemnim B and its related precursors are synthesized by two bacterial species via an unusual mechanism.

The researchers isolated the Tistrella mobilis and Tistrella bauzanensis from the Red Sea and Pacific Ocean respectively and found that both species produce compounds that are identical in structure to didemnin B and nordidemnin B, which were originally isolated from T. solidum.

A complete genome sequencing of T. mobilis revealed a cluster of 10 genes encoding an enzyme complex that synthesizes didemnin X and didemnin Y, biochemical precursors to didemnin B.

The gene cluster is not contained on the bacterial chromosome, but rather on a circular DNA molecule called a plasmid.

Using a technique called imaging mass spectrometry, the researchers determined that didemnin X and didemnin Y are secreted from the cell and then converted to didemnin B in an as yet unknown mechanism.

The results suggest that didemnin B could be produced by other bacterial species as the gene cluster encoding the didemnin B-synthesizing enzyme is located in plasmids can be passed between bacteria.

The complete T. mobilis genome could also lead to the production of renewable supplies of natural didemnin B and genetically engineered derivatives.

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