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. 2021 Oct 15;23(20):7819-7823.
doi: 10.1021/acs.orglett.1c02836. Epub 2021 Sep 28.

Biosynthesis of the Fusarium Mycotoxin (-)-Sambutoxin

Eun Bin Go  1 , Lee Joon Kim  1 , Hosea M Nelson  1   2 , Masao Ohashi  3 , Yi Tang  1   3
Affiliations

Biosynthesis of the Fusarium Mycotoxin (-)-Sambutoxin

Eun Bin Go et al. Org Lett. .

Abstract

4-Hydroxy-2-pyridone alkaloids have attracted attention for synthetic and biosynthetic studies due to their broad biological activities and structural diversity. Here, we elucidated the pathway and chemical logic of (-)-sambutoxin (1) biosynthesis. In particular, we uncovered the enzymatic origin of the tetrahydropyran moiety and showed that the p-hydroxyphenyl group is installed via a late-stage, P450-catalyzed oxidation of the phenylalanine-derived side chain rather than via a direct incorporation of tyrosine.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
4-Hydroxy-2-pyridone natural products. (A) Structures of (−)-sambutoxin (1) and related compounds; (B) Retrobiosynthesis of 1 suggests incorporation of tyrosine by the pathway.
Figure 2.
Figure 2.
Biosynthetic pathway to 1. (A) A conserved biosynthetic gene cluster from various species of Fusarium is proposed to be involved in the biosynthesis of 1. (B) Proposed biosynthetic pathway for 1 based on step-wise reconstitution.
Figure 3.
Figure 3.
MicroED structure of 13.
See this image and copyright information in PMC

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