Enzymes are enriched in bacterial essential genes

Abstract

Essential genes, those indispensable for the survival of an organism, play a key role in the emerging field, synthetic biology. Characterization of functions encoded by essential genes not only has important practical implications, such as in identifying antibiotic drug targets, but can also enhance our understanding of basic biology, such as functions needed to support cellular life. Enzymes are critical for almost all cellular activities. However, essential genes have not been systematically examined from the aspect of enzymes and the chemical reactions that they catalyze. Here, by comprehensively analyzing essential genes in 14 bacterial genomes in which large-scale gene essentiality screens have been performed, we found that enzymes are enriched in essential genes. Essential enzymes have overrepresented ligases (especially those forming carbon-oxygen bonds and carbon-nitrogen bonds), nucleotidyltransferases and phosphotransferases, while have underrepresented oxidoreductases. Furthermore, essential enzymes tend to associate with more gene ontology domains. These results, from the aspect of chemical reactions, provide further insights into the understanding of functions needed to support natural cellular life, as well as synthetic cells, and provide additional parameters that can be integrated into gene essentiality prediction algorithms.

Figure 1. Enzymes are enriched in bacterial essential genes.

(A) Averaged percentage of enzymes in essential and non-essential genes. (B) Percentages of enzymes in the 14 genomes in which large-scale gene essentiality screens have been performed.

Figure 2. Distribution of enzyme classes for essential and non-essential genes.

(A) Enzymes are classified into 1 of the 6 classes, oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases. The proportion of oxidoreductases is significantly lower, while that of ligases is significantly higher in essential than in non-essential genes. (B) Percentages of oxidoreductases and (C) ligases in the 14 genomes studied.

Figure 3. Significantly over- and under-represented second level enzyme types in essential genes.

Significantly over- and under-represented second level enzyme types of (A) EC 1.1: oxidoreducatases acting on the CH-OH group of donors (B) EC 3.2: glycosylases (C) EC 6.1: ligases forming carbon-oxygen bonds and (D) EC 6.3: ligases forming carbon-nitrogen bonds, in essential genes.

Figure 4. Significantly enriched third level enzyme types in essential genes.

Significantly enriched third enzyme types of (A) EC 6.1.1: ligases forming aminoacyl-tRNA (B) EC 2.7.7: nucleotidyltransferases (C) EC 2.7.4: phosphotransferases with a phosphate group as acceptor, in essential genes.

Figure 5. Essential enzymes are associated with more gene ontology domains.

Based on gene ontology, genes can be assigned 3 GO domains, molecular function, biological process and cellular component, which are independent of each other. (A) Essential enzymes have higher proportion of 3-GO-domain and lower proportion of 1&2-GO-domain containing genes. (B) Percentages of 1&2-GO-domain and (C) 3-GO-domain containing genes in essential and non-essential enzymes.

Figure 6. Overrepresentation of EC 2.7.7 and EC 2.7.4 in essential genes involved in pyrimidine metabolism pathway.

Part of the pyrimidine metabolism map is shown. The DAVID database was used to identify pathways in which essential genes are enriched, using E. coli as an example. Red rectangles denote reactions involving essential genes; filled yellow and blue boxes represent EC 2.7.7 (nucleotidyltransferase) and EC 2.7.4 (phosphotransferase), respectively.