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A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Function-oriented biosynthesis of beta-lactone proteasome inhibitors in Salinispora tropica
Markus Nett1, Tobias A M Gulder, Andrew J Kale
1Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093, USA.
Abstract:
The natural proteasome inhibitor salinosporamide A from the marine bacterium Salinispora tropica is a promising drug candidate for the treatment of multiple myeloma and mantle cell lymphoma. Using a comprehensive approach that combined chemical synthesis with metabolic engineering, we generated a series of salinosporamide analogues with altered proteasome binding affinity. One of the engineered compounds is equipotent to salinosporamide A in inhibition of the chymotrypsin-like activity of the proteasome yet exhibits superior activity in the cell-based HCT-116 assay.
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