Scale-up and Optimization of Natural Product Fermentation Processes using Mass-Guided Metabolite Fingerprinting

James A Zahn

doi:10.19080/aibm.2017.03.555614

Abstract

Scale-up and Optimization of Natural Product Fermentation Processes using Mass-Guided Metabolite Fingerprinting

Highlights

Microbial secondary metabolites represent a rich, chemically-diverse source of bioactive compounds that have been exploited for applications in human medicine, agriculture, and industry [1,2,3]
Changes in this workflow have been driven by wide scale adoption of miniaturized high-throughput screening technology (HTS) that has significantly reduced the sample volume that is available for parallel discovery efforts, and has increased the difficulty in achieving equivalent chemical output of bioactive metabolites during scale-up fermentation processes [6,7]
Standard solution showed a normal distribution for data points with a mean of 0.78 relative chemical similarity units and a standard deviation of 0.020rsu. This similarity coefficient value was similar to the value reported by Julian et al [14] for repeated injections of a tylosin-containing extract. This value (0.78±0.020 rsu) represents the maximum chemical similarity that can be achieved for analysis of experimental samples

Summary

Introduction

Microbial secondary metabolites represent a rich, chemically-diverse source of bioactive compounds that have been exploited for applications in human medicine, agriculture, and industry [1,2,3]. Natural product discovery groups have become increasingly focused on optimization of scale-up processes to successfully re-supply target-directed biological assays, and subsequent structural elucidation efforts to structurally-characterize bioactive compounds [3,5]. Changes in this workflow have been driven by wide scale adoption of miniaturized high-throughput screening technology (HTS) that has significantly reduced the sample volume that is available for parallel discovery efforts, and has increased the difficulty in achieving equivalent chemical output of bioactive metabolites during scale-up fermentation processes [6,7]. Once novel bioactive compounds have been identified using HTS approaches, the producing microorganism is transferred to larger volume fermentation

Objectives

Methods

Results