Tetronate antibiotics, a growing family of natural products featuring a characteristic tetronic acid moiety, are of importance and of particular interest for their typical structures, especially the spirotetronate structure, and corresponding versatile biological activities. Considerable efforts have persistently performed since the first tetronate was isolated, to elucidate the biosynthesis of natural tetronate products, by isotope-labeled feeding experiments, genetical characterization of biosynthetic gene clusters, and biochemical reconstitution of key enzymatic catalyzed reactions. Accordingly, the biosynthesis of spirotetronates has been gradually determined, including biosynthesis of a polyketide-derived backbone for spirotetronate aglycone, incorporation of a glycerol-derived three-carbon unit into tetronic acid moiety, formation of mature aglycone via Diels-Alder-like reaction, and decorations of aglycone with various deoxysugar moieties. In this paper, the biosynthetic investigations of natural tetronates are well documented and a common biosynthetic route for this group of naturalproducts is summarized accordingly.

The identity and reactivity of the intermediates in agglomerin biosynthesis were established and the respective roles of the acetyltransferase Agg4 and the eliminating enzyme Agg5 identified. It is proposedthat enzymes homologous to Agg4 and Agg5 carry out the dehydration steps in all spirotetronate biosynthetic pathways. If this proves correct, it may assist engineering ofthese pathways.