Katayama, T.; Hosogi, N.; Meng, X.-Y.; Kamagata, Y.; Tamaki, H.; Nobu, M. K.

Cellular metabolism is widely understood as an integrated network of redox reactions, energy conservation, and biosynthetic pathways. Here we show that across diverse prokaryotic lineages, loss of redox-associated functions is coupled with loss of nucleotide biosynthesis, raising a fundamental question of how such metabolically reduced organisms sustain cell growth. One of the most widespread and diverse lineages of prokaryotes, Minisyncoccota or Patescibacteriota, constitutes the majority of lineages exhibiting this pattern. To investigate how such organisms persist, we cultivated and characterized a representative of this lineage from a deep aquifer. The organism attaches to and penetrates growing bacterial host cells, and directly uptakes host RNA, concomitant with its depletion in the host. The metabolically reduced parasite cleaves host-derived RNA to directly supply cellular energy currencies and precursors for RNA/DNA synthesis, NTPs, without invoking canonical metabolic pathways. Codon usage in the parasite is complementary to that of its host, potentially minimizing translation of host-derived mRNA. Comparative genomics and phylogenetics indicate that these features are widespread and likely ancestral across the lineage. Exploitation of host RNA as a metabolic resource reveals a previously unrecognized metabolic strategy that demonstrates cellular metabolism can be sustained through direct utilization of informational macromolecules and thereby taps into an omnipresent energy reservoir, potentially supporting the environmental ubiquity of the metabolically reduced lineage.