Lipstatin

Lipstatin

Lipstatin is a potent natural product of Streptomyces toxytricini. It is a lipase inhibitor and the biogenesis of the semi-synthetic anti-obesity agent Orlistat. Lipstatin was first isolated in 1987 by Hans Zähner and his team.

History

Lipstatin was first isolated from the fermentation broth of Streptomyces toxytricini in 1987 by a team of researchers led by Hans Zähner. The team was searching for new antibiotics and enzyme inhibitors when they discovered lipstatin.

Structure and Properties

Lipstatin is a complex molecule with a unique structure. It is a 20-carbon fatty acid that is linked to a tetrahydrolipstatin core. This core is a highly functionalized cyclic ether that contains a hydroxyl group and a carboxylic acid group. The molecule also contains a lactone ring.

Biological Activity

Lipstatin acts as a potent, irreversible inhibitor of pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. By inhibiting this enzyme, lipstatin prevents the hydrolysis of triglycerides, thereby reducing the absorption of dietary fat.

Clinical Use

The semi-synthetic derivative of lipstatin, orlistat, is used clinically as an anti-obesity agent. Orlistat is marketed under the trade names Xenical and Alli.

Synthesis

The total synthesis of lipstatin has been achieved by several research groups. The first total synthesis was reported in 1990 by a team led by Robert M. Williams.

See Also

• Orlistat
• Lipase inhibitor
• Streptomyces toxytricini
• Hans Zähner