Allantofuranone Biosynthesis and Precursor-Directed Mutasynthesis of Hydroxylated Analogues

TL;DR

Scientists uncovered how a natural compound called allantofuranone is made and created new versions of it with added hydroxyl groups.

Contribution

The study reveals the biosynthetic pathway of allantofuranone and generates novel hydroxylated analogs through precursor-directed mutasynthesis.

Findings

The biosynthetic route of allantofuranone was elucidated using genome mining and heterologous expression in Aspergillus oryzae.

Combinatorial biosynthesis produced new natural products like deoxyascocorynin, hydroxyterferol, and hydroxyallantofuranone.

AlfB was identified as the enzyme responsible for oxidative cleavage and contraction of the quinol moiety.

Abstract

Genome mining and heterologous reconstitution
of biosynthetic
genes
in Aspergillus oryzae enabled elucidation
of the hitherto elusive biosynthetic route that produces allantofuranone
(1), a bioactive natural product originally isolated
from Allantophomopsis lycopodina. The
core non-ribosomal peptide synthetase (NRPS)-like enzyme AlfA of the alf BGC produces polyporic acid (2) from phenylpyruvic
acid. In subsequent reactions, compound 2 is reductively
dehydrated by the bifunctional enzyme AlfC and methylated by AlfD
to produce terferol (6). In a final step, the quinol
moiety of compound 6 is oxidatively cleaved and contracted
by the aromatic ring cleavage dioxygenase AlfB. Using combinatorial
biosynthesis, we were able to manipulate the biosynthetic route to
yield hydroxylated pathway congeners, most notably the new natural
products deoxyascocorynin (10), hydroxyterferol (11), and hydroxyallantofuranone (12).

Figures