Translating biosynthetic gene clusters into fungal armor and weaponry


Filamentous fungi are renowned for the production of a diverse array of secondary metabolites (SMs) where the genetic material required for synthesis of a SM is typically arrayed in a biosynthetic gene cluster (BGC). These natural products are valued for their bioactive properties stemming from their functions in fungal biology, key among those protection from abiotic and biotic stress and establishment of a secure niche. The producing fungus must not only avoid self-harm from endogenous SMs but also deliver specific SMs at the right time to the right tissue requiring biochemical aid. This review highlights functions of BGCs beyond the enzymatic assembly of SMs, considering the timing and location of SM production and other proteins in the clusters that control SM activity. Specifically, self-protection is provided by both BGC-encoded mechanisms and non-BGC subcellular containment of toxic SM precursors; delivery and timing is orchestrated through cellular trafficking patterns and stress- and developmental-responsive transcriptional programs.

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Figure 1: Fungal BGCs can contain genes encoding one or more self-protective devices.


Figure 2: Subcellular trafficking models for biosynthesis of aflatoxin, penicillin and trichothecene.


Figure 3: A transcriptional conduit from LaeA to BrlA regulates production of spore secondary metabolites.



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This work was supported by US National Institutes of Health R01 Al065728-09 and R01GM112739-01 to N.P.K.

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Correspondence to Nancy P Keller.

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Keller, N. Translating biosynthetic gene clusters into fungal armor and weaponry. Nat Chem Biol 11, 671–677 (2015).

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