Engineered Biosynthesis of Antiprotealide and Other Unnatural Salinosporamide Proteasome Inhibitors

Abstract
A new shunt in the phenylalanine biosynthetic pathway to the nonproteinogenic amino acid l-3-cyclohex-2′-enylalanine was exploited in the marine bacterium Salinispora tropica by mutagenesis to allow for the genetic engineering of unnatural derivatives of the potent proteasome inhibitor salinosporamide A (2) such as antiprotealide (1).

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