Chemoenzymatic synthesis of cryptophycin/arenastatin natural products

Zachary Q. Beck, Courtney Aldrich, Nathan A. Magarvey, Gunda Georg, David H. Sherman

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Microbially derived modular polyketide synthase and nonribosomal peptide synthetase biosynthetic pathways are a rich source of novel natural products. Development of these systems for the engineered biosynthesis of diverse secondary metabolites continues to progress as a robust source of chemical diversity. Recent efforts that employ individual enzymes and catalytic domains for the production or modification of small molecules have met with growing success. In this study, the thioesterase domain from the cryptophycin biosynthetic pathway was isolated and its function evaluated with a series of linear chain elongation intermediates in developing a novel chemoenzymatic synthesis of the cryptophycin/ arenastatin class of antitumor agents. The results show the high efficiency of the thioesterase in generating the 16-membered depsipeptide ring of this important natural product system. Moreover, analysis of selected substrates revealed considerable tolerance for structural variation within the seco-cryptophycin unit C β-alanine residue, but strict structural requirements at the phenyl group position of the unit A δ-hydroxy octadienoate chain elongation intermediates.

Original languageEnglish (US)
Pages (from-to)13457-13466
Number of pages10
Issue number41
StatePublished - Oct 18 2005


Dive into the research topics of 'Chemoenzymatic synthesis of cryptophycin/arenastatin natural products'. Together they form a unique fingerprint.

Cite this