Comparative genomic analysis reveals 2-oxoacid dehydrogenase complex lipoylation correlation with aerobiosis in archaea

Metagenomic analyses have advanced our understanding of ecological microbial diversity, but to what extent can
metagenomic data be used to predict the metabolic capacity of difficult-to-study organisms and their abiotic environmental
interactions? We tackle this question, using a comparative genomic approach, by considering the molecular basis of
aerobiosis within archaea. Lipoylation, the covalent attachment of lipoic acid to 2-oxoacid dehydrogenase multienzyme
complexes (OADHCs), is essential for metabolism in aerobic bacteria and eukarya. Lipoylation is catalysed either by lipoate
protein ligase (LplA), which in archaea is typically encoded by two genes (LplA-N and LplA-C), or by a lipoyl(octanoyl)
transferase (LipB or LipM) plus a lipoic acid synthetase (LipA). Does the genomic presence of lipoylation and OADHC genes
across archaea from diverse habitats correlate with aerobiosis? First, analyses of 11,826 biotin protein ligase (BPL)-LplA-LipB
transferase family members and 147 archaeal genomes identified 85 species with lipoylation capabilities and provided
support for multiple ancestral acquisitions of lipoylation pathways during archaeal evolution. Second, with the exception of
the Sulfolobales order, the majority of species possessing lipoylation systems exclusively retain LplA, or either LipB or LipM,
consistent with archaeal genome streamlining. Third, obligate anaerobic archaea display widespread loss of lipoylation and
OADHC genes. Conversely, a high level of correspondence is observed between aerobiosis and the presence of LplA/LipB/
LipM, LipA and OADHC E2, consistent with the role of lipoylation in aerobic metabolism. This correspondence between
OADHC lipoylation capacity and aerobiosis indicates that genomic pathway profiling in archaea is informative and that well
characterized pathways may be predictive in relation to abiotic conditions in difficult-to-study extremophiles. Given the
highly variable retention of gene repertoires across the archaea, the extension of comparative genomic pathway profiling to
broader metabolic and homeostasis networks should be useful in revealing characteristics from metagenomic datasets
related to adaptations to diverse environments.