Purine biosynthesis in archaea: variations on a theme

Abstract

BackgroundThe ability to perform de novo biosynthesis of purines is present in organisms in all three domains of life, reflecting the essentiality of these molecules to life. Although the pathway is quite similar in eukaryotes and bacteria, the archaeal pathway is more variable. A careful manual curation of genes in this pathway demonstrates the value of manual curation in archaea, even in pathways that have been well-studied in other domains.ResultsWe searched the Integrated Microbial Genome system (IMG) for the 17 distinct genes involved in the 11 steps of de novo purine biosynthesis in 65 sequenced archaea, finding 738 predicted proteins with sequence similarity to known purine biosynthesis enzymes. Each sequence was manually inspected for the presence of active site residues and other residues known or suspected to be required for function.Many apparently purine-biosynthesizing archaea lack evidence for a single enzyme, either glycinamide ribonucleotide formyltransferase or inosine monophosphate cyclohydrolase, suggesting that there are at least two more gene variants in the purine biosynthetic pathway to discover. Variations in domain arrangement of formylglycinamidine ribonucleotide synthetase and substantial problems in aminoimidazole carboxamide ribonucleotide formyltransferase and inosine monophosphate cyclohydrolase assignments were also identified.Manual curation revealed some overly specific annotations in the IMG gene product name, with predicted proteins without essential active site residues assigned product names implying enzymatic activity (21 proteins, 2.8% of proteins inspected) or Enzyme Commission (E. C.) numbers (57 proteins, 7.7%). There were also 57 proteins (7.7%) assigned overly generic names and 78 proteins (10.6%) without E.C. numbers as part of the assigned name when a specific enzyme name and E. C. number were well-justified.ConclusionsThe patchy distribution of purine biosynthetic genes in archaea is consistent with a pathway that has been shaped by horizontal gene transfer, duplication, and gene loss. Our results indicate that manual curation can improve upon automated annotation for a small number of automatically-annotated proteins and can reveal a need to identify further pathway components even in well-studied pathways.ReviewersThis article was reviewed by Dr. Céline Brochier-Armanet, Dr Kira S Makarova (nominated by Dr. Eugene Koonin), and Dr. Michael Galperin.

Resilience of biochemical activity in protein domains in the face of structural divergence

“…This domain displays a complex fold with a 5-stranded unit at the “top”, a smaller central sheet comprised of 3 strands, and a “bottom” formed by a mixed α+β structure related to the equivalent unit of the ATP-grasp fold [7,34]; all three units contribute residues for nucleotide binding or catalysis (Figure 3). Phyletic pattern and structural analysis [35] suggests that the most ancient version of this fold is likely to be the SAICAR synthetase (PurC), which is a kinase catalyzing the formation of a peptide-like bond in purine biosynthesis. Here, the “bottom” element has an extended sheet of 5 strands [36] (Figure 3A).…”

Predominant Acidilobus-Like Populations from Geothermal Environments in Yellowstone National Park Exhibit Similar Metabolic Potential in Different Hypoxic Microbial Communities

“…pernix, S. marinus, and H. butylicus) that are unable to synthesize purines de novo (88). Purines are important precursors for the synthesis of the molybdopterin cofactor necessary for Fdh-H.…”

SurR is a master regulator of the primary electron flow pathways in the order Thermococcales

“…Another noticeable trend in the transcriptional profiles in response to S 0 addition among the control and mutant SurR strains is the differential regulation of about 20 to 25 genes involved in purine biosynthesis (see Supporting Information Fig. S1 for purine biosynthetic pathway and gene organization) (Brown et al, 2011). In the control strain, expression of these genes increases at 10 min after S 0 addition, and fluctuates down again at 30 min, while in DsurR their expression decreases at both 10 and 30 min.…”