Classical strain improvement screening

Product yield is very often a factor that limits the development of a natural product as a lead compound. Traditionally, both chemical synthesis and classical strain improvement technologies have been applied to overcome this limitation. As natural products are often molecules of high structural and stereochemical complexity, their total synthesis is usually difficult, and yields are low. Classical strain improvement represents an equally time-consuming and rather undirected process, during which numerous rounds of mutagenesis and subsequent screening are applied to obtain strains with improved production titers. 

A standardized work flow for strain acquisition, strain purification, primary characterization, and where necessary, classical strain improvement was initiated in our laboratories in 2(X)8 and designated the strain supply chain (SSC). The introduction of these four standardized systematic work processes has resulted in a faster and more resource-efficient development of new strains, both wild-type strains and classically improved strains, for new product development. It is presented here to serve as an inspiration for other groups seeking to systematize their strain-screening activities (Figure 10.1). 

Whether a biocatalyst consists either of an isolate from a natural environment, of a classically improved strain or of a strain improved by various types of genetic engineering, the biocatalyst that is obtained after a screening effort will eventually be applied in a process. In order to obtain sufficient amounts of active biocatalyst, the cells have to be produced by fermentation. 

This screening for the best substrate is probably the easiest method for a chemist of improving the bio transformation. Nevertheless, if expertise in the handling of microorganisms or if a microbiological facility is available, then the best strain for a certain reaction should be found by screening many different microorganisms or, alternatively, a strain can be improved by classical means, such as mutation, or by more modern recombination techniques. 

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