Recent advancements in the biosynthetic mechanisms for polyketide-derived mycotoxins

Abstract

Polyketides (PKs) are a large group of natural products produced by microorganisms and plants. They are biopolymers of acetate and other short carboxylates and are biosynthesized by multifunctional enzymes called polyketide synthases (PKSs). This review discusses the biosynthesis of four toxic PK, aflatoxins, fumonisins, ochratoxins (OTs), and zearalenone. These metabolites are structurally diverse and differ in their mechanisms of toxicity. However, they are all of concern in food safety and agriculture because of their toxic properties and their frequent accumulation in crops used for food and feed. The focus is on the recent advancements in the understanding of the molecular mechanisms for the biosynthesis of these mycotoxins. Several of the mycotoxin PKSs have been genetically and biochemically studied while other PKSs remain to be investigated. Multiple post-PKS modifications are often required for the maturation of the mycotoxins. Many of these modification steps for aflatoxins and fumonisins are well established while the post-PKS modifications for zearalenone and OTs remain to be biochemically characterized. More efforts are needed to completely illustrate the biosynthetic mechanisms for this important group of PKs.

Figure 1

Chemical structures of representative mycotoxins discussed in this review, including aflatoxin B₁ (1), fumonisin B₁ (2), ochratoxin A (3), zearalenone (4), deoxynivalenol (5, an example of trichothecenes).

Figure 2

The general domain organization of (A) non-reducing PKS (NR-PKS), (B) partially-reducing PKS (PR-PKS), and (C) highly-reducing PKS (HR-PKS).

Figure 3

Chemical structures of aflatoxins and analogs. A and B, general structures; C and D, functional moieties which have a saturated bond at C8/C9, additionally D has a hydroxyl group at C8.

Figure 4

Biosynthetic mechanism for the early steps of aflatoxins.

Figure 5

Biosynthetic mechanism for fumonisins. A, the biosynthetic pathway for FB₁; B, the PLP-dependent polyketide chain-releasing mechanism in fumonisin biosynthesis.

Figure 6

Chemical structures of ochratoxin analogs. A, general structures; B, the polyketide originated portion; C, the open lactone form.

Figure 7

A proposed biosynthetic mechanism for ochratoxin A.

Figure 8

Biosynthetic mechanism for zearalenone. A, the structure of zearalenone and its five main analogs; B, a proposed biosynthetic pathway for zearalenone.