Themed collection Engineering the biosynthesis of fungal natural products

Guest editors Russell Cox and Tobias Gulder introduce this Natural Products Reports themed issue summarizing recent progress in engineering the biosynthesis of fungal natural products.

This Highlight reviews previous discoveries of ribosomal peptides in fungi, groups these natural products into three distinct families based on their unique properties and outlines how to leverage these properties for genome mining.

Aspergilli are biosynthetically ‘talented’ micro-organisms and therefore the natural products community has continually been interested in the wealth of biosynthetic gene clusters (BGCs) encoding numerous secondary metabolites related to these fungi.

Reconstitution studies applying the 3-stage strategy to the synthesis of highly elaborated indole diterpenes are reviewed.

A large and diverse family of fungal compounds are those related to the anthraquinone emodin. By viewing this family as a whole and combining our genetic and chemical understanding, we gain detailed insights into their biosynthetic origins.

This review provides an overview of CRISPR/Cas-based strategies for biosynthetic gene cluster engineering in filamentous fungi.

We review studies from early isolation and elucidation to recent bioinformatics and in vitro work regarding the biosynthesis of maleidrides. These are dimeric anhydrides, made from monomers coupled in various modes leading to structural diversity.

Heterologous expression of biosynthetic gene clusters (BGCs) has become a widely used tool for genome mining of cryptic pathways, bottom-up investigation of biosynthetic enzymes, and engineered biosynthesis of new natural product variants.

Fungal nonribosomal peptides (NRPs) and the related polyketide–nonribosomal peptide hybrid products (PK–NRPs) are a prolific source of bioactive compounds, some of which have been developed into essential drugs.

The α-ketoglutarate dependent oxygenases catalyze remarkable chemistries in polyketide-derived fungal meroterpenoid biosynthesis. This review summarizes recent progress in the structure-based engineering of these enzymes.

This review summarises recent research on metobolic engineering approaches towards terpenes, including work to investigate unknown pathways and to improve accessibility of known compounds.

Current understanding of iterative highly programmed Type 1 PKS that control starter unit selection, chain length, methylation pattern, and stereochemistry.

Macrolides, which are widely found in plants and microorganisms, are polyketides constituted of different-sized rings lactones. They show different biological activities and the review focused on their isolation from fungi in the last four decades.

In their natural environment, fungi must compete for resources. It has been hypothesized that this competition likely induces the biosynthesis of secondary metabolites for defence.

Investigations into fungal polyketide biosynthesis have revealed many examples of megasynthases and trans-acting accessory enzymes. This review collates the different classes of collaborating enzymes, demonstrating common themes and rarer examples.

This review provides an overview of the current information on non-peptide secondary metabolites from poisonous mushrooms, focusing on their chemistry, bioactivity, and biosynthesis, highlighting their potential for drug development.

Since the early 1970s, 375 natural products have been identified from members of the fungus-farming termite symbiosis, and this review summarises and discusses the ecological implications of the presence of this vast chemical repertoire.