DNA microarray has emerged as a powerful technique for parallel detecting of all the mRNA levels in the cell. With this technology, transcription profiles at the genomic scale can be readily obtained. This technology has typically been applied to eukaryotic systems and medical problems. Here we demonstrated an application to microbial biotechnology, protein production in Escherichia coli. The gene expression pattern of the E. coli was determined during high level expression of a model protein, the a-subunit of luciferase (the luxA gene product). The whole set of E. coli genes was amplified and printed on a glass slide as a probe to determine the mRNA level of E. coli during overexpression of LuxA. With a proper statistical treatment, we found that at least 10% of E. coli genes were perturbed during protein overexpression. Almost all the known heat shock genes were up-regulated. Most of glucose transport and glycolytic genes were down-regulated. In addition, there are numerous genes up-or down-regulated that cannot be readily explained by existing mechanisms. These results offer an opportunity for further improvement of the host strain, growth medium, and bioprocessing conditions.