Thermophilic archaeon orchestrates temporal expression of GDGT ring synthases in response to temperature and acidity stress.

Glycerol dibiphytanyl glycerol tetraethers (GDGTs) are unique archaeal membrane-spanning lipids with 0-8 cyclopentane rings on the biphytanyl chains. The cyclization pattern of GDGTs is affected by many environmental factors, such as temperature and pH, but the underlying molecular mechanism remains elusive. Here, we find that the expression regulation of GDGT ring synthase genes grsA and grsB in thermophilic archaeon Sulfolobus acidocaldarius is temperature- and pH-dependent. Moreover, the presence of functional GrsA protein, or more likely its products cyclic GDGTs rather than the accumulation of GrsA protein itself, is required to induce GrsB expression, resulting in temporal regulation of GrsA and GrsB expression. Our findings establish a molecular model of GDGT cyclization regulated by environment factors in thermophilic ecosystem, which could be also relevant to that in mesophilic marine archaea. Our study will help better understand the biological basis for GDGTs-based paleoclimate proxies.