Chemoenzymatic Synthesis of Spinosyn A

Abstract

Following the biosynthesis of polyketide backbones by polyketide synthases (PKSs), post-PKS modifications result in a significantly elevated level of structural complexity that renders the chemical synthesis of these natural products challenging. We report herein a total synthesis of the widely used polyketide insecticide spinosyn A by exploiting the prowess of both chemical and enzymatic methods. As more polyketide biosynthetic pathways are characterized, this chemoenzymatic approach is expected to become readily adaptable to streamlining the synthesis of other complex polyketides with more involved post-PKS modifications.

Strategies for Enhancing the Yield of the Potent Insecticide Spinosad in Actinomycetes

“…However, four rhamnose biosynthesis genes (gtt, gdh, epi, and kre) are located outside the spinosyn gene cluster. [10][11][12][13][14][15][16][17][18][19][20][21] Spinosad is a potent insecticide with a huge potential market. However, the titer of spinosad in the original producer Sa.…”

The Application of Dioxygenase‐Based Chemoenzymatic Processes to the Total Synthesis of Natural Products

“…The capacity of biocatalysis to underpin or create sustainable chemical manufacturing processes represents yet another motivation for the development of chemoenzymatic methods and these have now been deployed in the production of, inter alia, carbohydrates, glycoproteins, polypetides (including for use as functional and structural materials), active pharmaceutical ingredients (APIs), agrochemicals and natural products…”

An unusual intramolecular trans-amidation

“…2 Within recent years, the fusion between synthetic organic chemistry and structural biology has provided a rich forum to further explore the mechanisms that guide each of the discrete operations during a biosynthetic process. 3 The significance of these advances has most recently allowed chemoenzymatic methods to address the total synthesis of complex natural products such as spinosyn A. 4 …”