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.