Process analysis of macrotetrolide biosynthesis during fermentation by means of direct infusion LC-MS.

The optimization of the biosynthetic pathways is highly attractive for the large-scale preparation of macrotetrolides, because overall yields in the chemical synthesis of compounds like nonactin have been very low. A key success factor determining the outcome of such optimizations is the adequate process analysis for the envisioned product. The analytical methods for process control involved in the past spectrophotometric and chromatographic measurements. LC-MS offers a modern approach to obtain more detailed data than the spectrophotometric and chromatographic measurements used in the past. In this work, a fast and versatile analytical LC-MS method has been set up, which has proven of much value for the in-process analysis of macrotetrolides during fermentation and which has allowed rapid large-scale bioprocess development.