1191041-40-3Relevant academic research and scientific papers
Biocatalytic synthesis of pikromycin, methymycin, neomethymycin, novamethymycin, and ketomethymycin
Hansen, Douglas A.,Rath, Christopher M.,Eisman, Eli B.,Narayan, Alison R. H.,Kittendorf, Jeffrey D.,Mortison, Jonathan D.,Yoon, Yeo Joon,Sherman, David H.
, p. 11232 - 11238 (2013)
A biocatalytic platform that employs the final two monomodular type I polyketide synthases of the pikromycin pathway in vitro followed by direct appendage of d-desosamine and final C-H oxidation(s) in vivo was developed and applied toward the synthesis of a suite of 12- and 14-membered ring macrolide natural products. This methodology delivered both compound classes in 13 steps (longest linear sequence) from commercially available (R)-Roche ester in >10% overall yields.
Synthesis and biochemical analysis of complex chain-elongation intermediates for interrogation of molecular specificity in the erythromycin and pikromycin polyketide synthases
Mortison, Jonathan D.,Kittendorf, Jeffrey D.,Sherman, David H.
experimental part, p. 15784 - 15793 (2010/01/30)
The 6-deoxyerythronolide B synthase (DEBS) and pikromycin (Pik) polyketide synthase (PKS) are unique multifunctional enzyme systems that are responsible for the biosynthesis of the erythromycin and pikromycin 14-membered ring aglycones, respectively. Together, these natural product biosynthetic systems provide excellent platforms to examine the fundamental structural and catalytic elements that govern polyketide assembly, processing, and macrocyclization. In these studies, the native pentaketide intermediate for DEBS was synthesized and employed for in vitro chemoenzymatic synthesis of macrolactone products in engineered monomodules Ery5, Ery5-TE, and Ery6. A comparative analysis was performed with the corresponding Pik module 5 (PikAIII) and module 6 (PikAIV), dissecting key similarities and differences between these highly related PKSs. The data revealed that individual modules in the DEBS and Pik PKSs possess distinctive molecular selectivity profiles and suggest that substrate recognition has evolved unique characteristics in each system.
