Serofendic acid is a natural neuroprotective molecule found in fetal calf serum. It is able to protect neurons against mechanisms of cell death associated with neurodegenerative disease. Because only trace quantities are present in fetal calf serum and complete chemical syntheses are long and inefficient, its development as a therapeutic agent has been slow. We engineered a heterologous metabolic pathway in Streptomyces to produce a late-stage synthetic intermediate, ent-atiserenoic acid, at high titers. We completed the total synthesis of serofendic acid from this intermediate in four steps.
Bibliographical noteFunding Information:
We thank Dr. Stephen Harvey from the UMN Mass Spectroscopy Center, Todd Rappe from the UMN NMR Center, and Dr. Victor Young Jr. from the UMN X-ray Crystallography Laboratory for their contributions in acquiring analytical data to support this work. MJS is supported in part by The Defense Advanced Research Projects Agency (grant number D17AP00028). The views, opinions, and/or findings contained in this article are those of the author and should not be interpreted as representing the official views or policies, either expressed or implied, of the Defense Advanced Research Projects Agency or the Department of Defense. SH and DP are supported in part by the Biocatalysis Initiative grant from the University of Minnesota Biotechnology Institute. SH is also supported by the Arnold H. Johnson Fellowship.
Copyright © 2019 American Chemical Society.
- metabolic engineering