Flavoaffinins, elusive cellulose-binding natural products from an anaerobic bacterium

Cellulose is the most abundant polymer on earth and plays a key role in the carbon cycle, agriculture, and human health. Many anaerobic cellulose-degrading bacteria produce uncharacterized yellow-orange, cellulose-binding pigments known as yellow affinity substances (here referred to as flavoaffinins) that are associated with efficient cellulose degradation. Here, we isolate and structurally characterize the flavoaffinins from Clostridium ( Hungateiclostridium ) thermocellum , a key workhorse for the industrial conversion of cellulosic feedstocks to ethanol. Flavoaffinins represent an unprecedented structural juxtaposition of an aryl polyene chain with a hydroxy-diene γ-lactone. We also shed light on their biosynthetic origins using stable-isotope feeding experiments. This effort lays the groundwork for understanding the biological function(s) of the flavoaffinins and expands the limited number of natural products isolated from obligately anaerobic microbes.