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From searching for the needle in the haystack to searching the haystack
Directed evolution - the interplay of generating diversity and selecting the fittest variant for a possible next round of diversification - has been a major engine for the advancement of biotechnology from the first days until today. Two processes had recently major influences on the intensity with which we can undertake directed evolution - DNA synthesis and microfluidics. Our ability to build more precise libraries has drastically increased the information content that we can survey in a round of selection, and microfluidics has drastically increased the throughput with which we can do the surveying. I will discuss the importance and impacts of these processes on the development of biocatalysts for modern biotechnology and illustrate the discussion with recent results from our own work on enzymes, industrial production strains, and the search for novel antibiotics. While classical efforts are based on screening and selection, combination of modern screening methods with next generation sequencing opens new horizons to catalyst development, as it allows to go from cherry-picking to generating data sets that can be sufficiently large for machine learning.