Impact of lifestyle on cytochrome P450 monooxygenase repertoire is clearly evident in the bacterial phylum Firmicutes

Abstract

Cytochrome P450 monooxygenases (CYPs/P450s), heme thiolate proteins, are well known for their role in organisms' primary and secondary metabolism. Research on eukaryotes such as animals, plants, oomycetes and fungi has shown that P450s profiles in these organisms are affected by their lifestyle. However, the impact of lifestyle on P450 profiling in bacteria is scarcely reported. This study is such an example where the impact of lifestyle seems to profoundly affect the P450 profiles in the bacterial species belonging to the phylum Firmicutes. Genome-wide analysis of P450s in 972 Firmicutes species belonging to 158 genera revealed that only 229 species belonging to 37 genera have P450s; 38% of Bacilli species, followed by 14% of Clostridia and 2.7% of other Firmicutes species, have P450s. The pathogenic or commensal lifestyle influences P450 content to such an extent that species belonging to the genera Streptococcus, Listeria, Staphylococcus, Lactobacillus, Lactococcus and Leuconostoc do not have P450s, with the exception of a handful of Staphylococcus species that have a single P450. Only 18% of P450s are found to be involved in secondary metabolism and 89 P450s that function in the synthesis of specific secondary metabolites are predicted. This study is the first report on comprehensive analysis of P450s in Firmicutes.

Figure 1

Analysis of P450s in Firmicutes species. Comparative analysis of P450s at species level (A), subphylum level (B) and genera level (C) is presented in the figure. Owing to the availability of few species genomes belonging to the other five subphyla of Firmicutes (Erysipelotrichia, Limnochordia, Negativicutes, Thermolithobacteria, and Tissierellia), these species were kept under “Others” at KEGG. Thus, we indicated the P450 profiles in these species under the name Other species. Numbers next to the bars indicate the number of species. Detailed information on Firmicutes species P450 profiles is presented in Table S1.

Figure 2

Phylogenetic tree of Firmicutes species P450s. Different P450 families are indicated with different colours. A high-resolution phylogenetic tree is provided in Supplementary Dataset 2.

Figure 3

Analysis of presence of P450 family (red) or its absence (green) in 229 Firmicutes species. Two hundred and twenty-nine Firmicutes species form the horizontal axis and P450 family numbers form the vertical axis. The data used in the generation of this figure are presented in Supplementary Dataset 3.

Figure 4

Comparative analysis of P450s associated with secondary metabolism in Firmicutes species. (A) Comparative analysis of P450 families that are part of secondary metabolite biosynthetic gene clusters (BGCs). The P450 family name, number of P450s and their percentage of the total number of P450s part of BGCs are presented in the figure. (B) Comparative analysis of types of BGCs. The number at the top of each bar represents the number of P450s in the type of BGC. (C) Comparative analysis of most similar known clusters that have P450s. The number at the top of each bar represents the total number of similar clusters. Detailed information is presented in Table S2.