Functional annotation of operome from Methanothermobacter thermautotrophicus ΔH: An insight to metabolic gap filling

Methanothermobacter thermautotrophicus ΔH (MTH) is a potential methanogen known to reduce CO₂ with H₂ for producing methane biofuel in thermophilic digesters. The genome of this organism contains ~50.5% conserved hypothetical proteins (HPs; operome) whose function is still not determined precisely. Here, we employed a combined bioinformatics approach to annotate a precise function to HPs and categorize them as enzymes, binding proteins, and transport proteins. Results of our study show that 315 (35.6%) HPs have exhibited well-defined functions contributing imperative roles in diverse cellular metabolism. Some of them are responsible for stress-response mechanisms and cell cycle, membrane transport, and regulatory processes. The genome-neighborhood analysis found five important gene clusters (dsr, ehb, kaiC, cmr, and gas) involving in the energetic metabolism and defense systems. MTH operome contains 223 enzymes with 15 metabolic subsystems, 15 cell cycle proteins, 17 transcriptional regulators and 33 binding proteins. Functional annotation of its operome is thus more fundamental to a profound understanding of the molecular and cellular machinery at systems-level.