Microorganisms such as yeasts, fungi and bacteria are used extensively in the preparation of foodstuffs. The carefully controlled use of food-grade bacteria plays an important role in starter cultures (mainly lactic acid bacteria) and in the production of specific metabolites and other ingredients. In addition, so-called `probiotic' bacteria are added to some foods in an attempt to enhance human health. In contrast, any unintentional microbial contamination of food can adversely affect food safety and shelf-life.

Numerous bacterial genomes have been fully sequenced in the past few years, and the information content of genome databases is increasing rapidly. The initial focus was on medically important pathogens, such as Haemophilus influenzae, Helicobacter pylori, E. coli, Mycobacterium tuberculosis, etc., but more recently a number of bacteria related to food production have been fully sequenced, or are nearing completion. Gram-positive bacteria in particular play a pivotal role in various aspects of food fermentation, ingredient production and food safety.

Professor Siezen's group is studying the genomes of food-relevant bacteria in a collaboration with groups at: NIZO Food Research (Ede); the Wageningen Center for Food Sciences (Wageningen); and the Centre for Molecular and Biomolecular Informatics (Nijmegen). The main approach is to use various bioinformatical tools to analyse and compare genes, gene clusters, encoded proteins, biochemical pathways, regulatory mechanisms, and so on. We use the most advanced bioinformatical tools, for functional annotation of genes, comparative genomics, and functional and structural prediction of encoded proteins.

The genomes of several lactic acid bacteria are being studied, in collaboration with NIZO Food Research and the Wageningen Center for Food Sciences (WCFS), who are sequencing a Lactobacillus genome. In the immediate future, research in this area will involve:

• identification of genes and functional annotation of the Lactobacillus genome
• mapping of the metabolic and biosynthetic pathways, and regulatory elements of Lactobacillus
• comparative genomics of lactic acid bacteria (various species of Lactobacillus, Lactococcus, Bifidobacterium, Streptococcus). This should lead to insights into the conservation and variability of gene and protein sequences, gene ordering and clustering, metabolic pathways, regulatory mechanisms, and so on.

This research aims to reconstruct the cellular processes, metabolic potential and regulatory networks of selected gram-positive Bacteria and Archaea, by in silico analysis of all proteins encoded by their chromosome. The results will be incorporated into “virtual cell” databases.

The genomes of gram-positive food pathogens and spoilage bacteria are being compared, by data mining in genome databases. In the immediate future, research in this area will include:

• comparative genomics of gram-positive food pathogens and spoilage bacteria (e.g. Listeria monocytogenes, Enterococcus faecalis, Streptococcus sp., Bacillus cereus, Clostridium difficile)
• comparative genomics of these gram-positive bacteria with gram-negative pathogenic and food spoilage bacteria (e.g. E. coli K12, Salmonella, Campylobacter).

Subtilisin-like serine proteases are found in many prokaryotes, archaea and eukaryotes. In the immediate future, research in this area will include:

• pattern and context searching for subtilases in microbial genomes
• homology modelling of subtilases.