Glycosylation and production characteristics of epothilones in alkali-tolerant Sorangium cellulosum strain So0157-2

Abstract

3-O-alpha-D-ribofuranosyl epothilone A (epothiloneoside A) is a major component of glycosylated epothilones in Sorangium cellulosum strain So0157-2. The production and glycosylation ratios of epothiloneoside A in both solid and liquid culture conditions with various pH values and carbon sources were studied. The results showed that glycosylation occurs whenever epothilones are produced, regardless of changes in pH values, production time curves, and different carbon sources. We suggest that glycosylation is a stable process, paralleling the biosynthesis of epothilones in the So0157-2 strain.

Enzymatic synthesis of epothilone A glycosides

“…2D-NMR analyses were carried out to further confirm the glucosylation position. The 1 H– 1 H COSY NMR analysis (Additional file 1: Figure S2 (B)) showed that the anomeric proton ( δ  = 4.49 ppm) was in a close relationship with δ  = 3.2 ppm, which was annotated to H-6 of epothilone by comparing our data with 1 H NMR of previously identified epothilone A and pentoside of epothilone as epothiloneoside A by Zhao et al [2010]. Different hydroxylated and epoxidated epothilone A have been produced by microbial biotransformation using Aspergillus niger (Wang et al [2009]) which were characterized by different NMR analyses.…”

“…Zhao and his group have successfully characterized a pentoside of epothilone A as epothiloneoside A in 2010 from Sorangium cellulosum So0157-2 (PCT/CN2008/001946) strain culture, and the glycosylated compound was detected as attachment of sugar in C-3 hydroxyl position with a molar mass of 625.29. The compound was determined to be 3- O - α -D-ribofuranosyl epothilone A (Zhao et al [2010]) beside this no other reports are available about glycosylated analogues of epothilone A.…”

“…Drugs that target microtubules are the most commonly prescribed anticancer therapeutics in current clinical practice. Epothilones bear similar potency and were classified as a new class of antimicrotubule agents that share the equipotent structural and functional properties with taxanes among which few have already passed preclinical studies as cancer therapeutic agents (Zhao et al [2010]; Goodin et al [2004]). Ixabepilone, a semisynthetic analog of epothilone B, was approved by the US Food and Drug Administration in October 2007 to treat metastatic or locally advanced breast cancer as monotherapy (Donovan and Vahdat [2008]).…”

A Novel Cold-Adapted Lipase from Sorangium cellulosum Strain So0157-2: Gene Cloning, Expression, and Enzymatic Characterization

“…The Sorangium cellulosum So0157-2 strain (the deposition ID in the China Center of Typical Culture Collection (CCTCC) is CCTCC M 208078) was cultured in liquid M26 medium at 30 °C as previously described [38]. E. coli Top10 and BL21 (DE3) were used as the cloning host and the expression host, and pMD-T simple vector (Takara, Dalian, China) and pET-22b (+) (Novagen, Darmstadt, Germany) were used as the cloning vector and the expression vector, respectively.…”

Extraordinary expansion of a Sorangium cellulosum genome from an alkaline milieu

“…So0157-2 produces epothilones, cytotoxic macrolides that stabilize microtubules, mimicking the effects of paclitaxel on cancer cells21. More than 20 epothilone derivatives have been identified in So0157-2, including a novel glycosylated epothilone, epoAG22, a promising candidate for clinical application. The strain is an alkaline-adaptive epothilone producer that grows across a wide pH range (5.0–14.0).…”