Abstract
Hydroquinone meroterpenoids, especially those derived from marine sponges, display a wide range of biological activities. However, use of these compounds is limited by their inaccessibility; there is no sustainable supply of these compounds. Furthermore, our knowledge of their metabolic origin remains completely unstudied. In this review, an in depth structural analysis of sponge merotriterpenoids, including the adociasulfate family of kinesin motor protein inhibitors, provides insight into their biosynthesis. Several key structural features provide clues to the relationships between compounds. All adociasulfates appear to be derived from only four different hydroquinone hexaprenyl diphosphate precursors, each varying in the number and position of epoxidations. Proton-initiated cyclization of these precursors can lead to all carbon skeletons observed amongst sponge merotriterpenoids. Consideration of the enzymes involved in the proposed biosynthetic route suggests a bacterial source, and a hypothetical gene cluster was constructed that may facilitate discovery of the authentic pathway from the sponge metagenome. A similar rationale can be extended to other sponge meroterpenoids, for which no biosynthetic pathways have yet been identified.
Highlights
Meroterpenes have long been recognized for their diverse biological activities
Marine sponges represent a prolific source of hydroquinone meroterpenoids, some of which exhibit unique activities that cannot be substituted for using alternative compounds
This review focuses on the merotriterpenoids, including the adociasulfates (Figure 1)
Summary
Meroterpenes have long been recognized for their diverse biological activities. In particular, hydroquinone meroterpenes are interesting because of their potential for redox chemistry and wide distribution in nature [1,2]. This review focuses on the merotriterpenoids, including the adociasulfates (Figure 1) This family includes several unique carbon skeletons, its members are frequently sulfated, and it encompasses a wide variety of biological activities. 2,3-dioxygenase, whose activity mediates T-cell activation and whose overexpression in cancer may prevent tumor rejection, is inhibited by halicloic acids A and B (15, 16) [5] Some of these compounds display weak antimicrobial activities [6,7]. Inhibition of kinesin by adociasulfate-2 (2) involves competition with microtubules for binding [11,12] This mode of kinesin inhibition is known for only two other compounds, rose bengal lactone and the polyoxometalate NSC 622124, which both display characteristic features of nonspecific inhibition, including aggregate formation, indiscriminate binding.
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