Paxillin biosynthesis

Figure 5.56 Early proposal for paxilline biosynthesis based on chemical identification of intermediates from filamentous fungi.

Figure 5.57 Schematic representation of the organization of the gene cluster responsible for paxilline biosynthesis in PenicilUum paxilli.

Subsequently, the intact incorporation of multiply H-labeled 3-geranylgeranylind ole 49b into paxilline proved that 3-geranylgeranylindole is a biosynthetic intermediate of indole-diterpenes (Figure 5.59) [256]. Thus, the proposal for the early steps of paxilline biosynthesis involves the formation of 3-geranylgeranylindole 49a catalyzed by GGPP synthase, subsequent epoxidation, and cationic cyclization to produce emindole SB. 

Figure 5.59 Revision of the early steps of the paxilline biosynthesis.

Figure 5.58 Proposed pathway for the biosynthesis of paxilline showing steps catalyzed by PaxG (geranylgeranyl diphosphate synthase), PaxP (cytochrome P450 monooxygenase), and PaxQ (cytochrome P450 monooxygenase).

Tanabe (1976) and Acklin et al. (1976) studied the biosynthesis of paxilline by employing C-labeled precursors and NMR spectroscopy. Tanabe proposed a biosynthetic scheme (scheme 3) for paxilline based on the results obtained from labeling experiments with [l,2- C]acetate and analysis of the product. 

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