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An attempt to describe the nature of the surface-active substances of the eustachian tube lining layer that influence normal tubal function was undertaken. Under sterile conditions, guinea pig tubotympanic washings were collected, centrifuged, and pooled. Analysis of the pooled lavages using standard surface chemistry techniques confirmed the presence of significant surface-tension-lowering activity in the mucous lining layer of the eustachian tube, but the surface pressure obtained is neither as great nor displays the same degree of hysteresis as pulmonary surfactant. Following separation into aqueous and lipid fractions, measurable amounts of surface activity can be found in both isolates. The chemical composition and concentration of the lipid fraction, and its relative contribution to the surface activity of the tubotympanic washings, however, is smaller and radically different from the phospholipids found in surfactant. A significantly higher concentration of protein was recovered in comparison with the lipid portion, and it was observed that the surface activity of the total washings and the aqueous phase bore remarkable similarities. Although the surface-tension-lowering properties of the tubal lining layer may be the consequence of a combined synergistic action of the lipid and protein moieties, we believe that the current evidence points toward the proteins as being the primary tubal surface-tension-lowering substances.

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Fatty acyl-AMP ligases (FAALs) channelize fatty acids towards biosynthesis of virulent lipids in mycobacteria and other pharmaceutically or ecologically important polyketides and lipopeptides in other microbes. They do so by bypassing the ubiquitous coenzyme A-dependent activation and rely on the acyl carrier protein-tethered 4'-phosphopantetheine (holo-ACP). The molecular basis of how FAALs strictly reject chemically identical and abundant acceptors like coenzyme A (CoA) and accept holo-ACP unlike other members of the ANL superfamily remains elusive. We show FAALs have plugged the promiscuous canonical CoA-binding pockets and utilize highly selective alternative binding sites. These alternative pockets can distinguish adenosine 3', 5'-bisphosphate-containing CoA from holo-ACP and thus FAALs can distinguish between CoA and holo-ACP. These exclusive features helped identify the omnipresence of FAAL-like proteins and their emergence in plants, fungi, and animals with unconventional domain organisations. The universal distribution of FAALs suggests they are parallelly evolved with FACLs for ensuring a CoA-independent activation and redirection of fatty acids towards lipidic metabolites.