Classical Strain Improvement – Back to the Future!

Posted 9/8/11 by . Filed under Featured News.

Everybody is familiar, at least in passing, with classical strain improvement. You treat cells with a chemical or physical mutagen, kill off most in the process, and screen the survivors for that rare clone which produces more of the product you are interested in. This new strain becomes the starting point for a new round and you repeat the process. It is a bit more involved than that but you get the idea. You never really know why the strain is improved – unless you sequence the thing – but if you are in industry your job is to become rich (because you made more product cheaper) and not famous (because you published a paper).

In the era of metabolic engineering where scientists wanted to be more targeted in the way they improved the productivity of strains, classical strain improvement got the reputation of being too slow and too labor intensive for the improvements that were achieved. That might have been true 20 years ago but with the use of miniaturized cultivation along with automated colony picking and liquid handling; a large number of colonies can be screened regardless of whether their genetic variability was introduced by metabolic engineering or chemical mutagenesis.

Some companies have never forgotten the value of classical strain improvement. A paper given at the 2009 Recent Advances in Fermentation Technology Meeting (RAFT) described how Eli Lilly has used this approach for over fifty years to continually improve strains for in-line natural products. I saw the same thing at Merck for the continual improvement of avermectin and lovastatin producing strains.

It has been pleasantly surprising to see biology companies producing biofuels and renewable chemicals use classical strain improvement as a supplement to synthetic biology or other metabolic engineering approaches. Amyris is one such company to employ this approach as described in a paper given at the 2010 SIM annual meeting (oh, and by the way, didn’t they just have an IPO?). It may not be sexy but it is effective, efficient, and a great tool to have in the tool box.


About Neal Connors
Dr. Neal Connors is currently the owner/president of Phoenix BioConsulting, LLC (; a company providing consulting services to the fermentation, industrial microbiology, biotechnology, and legal sectors.

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