Nature biotechnologyJun 30, 2026

Using prime editing for accurate gene changes and controlling fungal metabolism

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 2, 2026

Abstract

An average editing efficiency approaching 90% was achieved using the fPE7max prime editing platform in filamentous fungi.

The fPE7max platform supports various types of genetic edits, including base substitutions and small insertions or deletions.
It allows for larger genetic modifications of up to 1 kb insertions and 10 kb deletions.
Editing the laeA gene affects metabolic output in multiple fungal species.
Metabolomic profiling identified 18 metabolites, including 8 previously unreported compounds.
Three of these metabolites exhibited cytotoxic activity.

Simplified

Prime editing has not been established in filamentous fungi, which are major ecological contributors and industrial hosts with vast biosynthetic capacity. Here we develop fPE7max, a prime editing platform optimized for fungi, which supports different edit types, including base substitutions and defined small insertions or deletions, with an average editing efficiency approaching 90%, across diverse genomic loci and species. fPE7max further enables larger insertions of up to 1 kb and deletions of up to 10 kb. We perturb upstream open reading frames in the pleiotropic regulator gene, laeA, to modulate metabolic output across multiple fungal species. Metabolomic profiling reveals activation of previously lowly biosynthetic pathways, leading to the identification of 18 metabolites, including 8, to our knowledge, previously unreported structures, 3 of which with cytotoxic activity. These results establish fPE7max as an efficient platform for genome engineering in filamentous fungi and show upstream open reading frame editing as a strategy for modulating endogenous regulatory networks and accessing the fungal chemical repertoire.