The use of metabolic engineering techniques to increase the productivity of primary and secondary metabolites within filamentous fungi

Filamentous fungi are multicellular eukaryotic microorganisms that primarily grow in nature with energy obtained via the degradation of macromolecules. Therefore, their capacity to produce hydrolytic enzymes is unusually high, which has vastly been exploited in the mass production of industrially relevant enzymes such as amylase, protease, lipase and so on. In 1917, it was discovered that Aspergillus niger had the capacity to produce large amounts of primary metabolites, a key one being citrate that is now ubiquitously used as an acidulent food additive. Filamentous fungi were thereafter intensively researched to identify the variety of primary metabolites they produced, and subsequently secondary metabolites which are now widely used as pharmaceutical agents (e.g. penicillin, lovastatin), pigments (e.g. Monascus pigment), platform chemicals (e.g. itaconic acid), cosmetics (e.g. kojic acid) and so on.

In the wider field of microbial production of valuable compounds, bacteria (e.g. Escherichia coli, Streptomyces sp., Corynebacterium sp., etc.) and other fungal species (e.g. Saccharomyces cerevisiae, Pichia pastoris, Yarrowia lipolytica, etc.), have been widely utilized as production hosts. However, when the genomes of model filamentous fungi wild-type strains were sequenced two decades ago, they emerged as having considerable merits due to their ability to degrade polymers, their availability in solid-state cultures, and their suitability to produce key primary and secondary metabolites. Nevertheless, challenges arose due to the difficulty to utilize them in high-density liquid cultures because of pellet formation, the laborious experiments required in their genetic manipulation compared to other host microorganisms, and the necessity of long periods of time for mutant construction via recombination. Therefore, the implementation of existing and development of new metabolic engineering techniques to overcome these challenges are essential to maximize the production of key primary and secondary metabolites.

This Research Topic is dedicated to breakthrough research on the production of primary and secondary metabolites via metabolic engineering in filamentous fungi as well as the variety of metabolic engineering techniques utilized in the process.
Techniques included for Gene Manipulation are:
- Homologous Recombination
- Genome Editing
Techniques included for Bottleneck Reaction Prediction are:
- Flux Balance Analysis (FBA)
- Omics (Transcriptomics, Metabolomics, Multi-Omics, Trans-Omics…etc.)

We seek Reviews or Mini-Reviews highlighting what has been achieved thus far, Original Research or Brief Research Reports demonstrating novel findings, and Perspective or Opinion papers illustrating the promising progress this area of research can attain in the near future.

Keywords: Filamentous fungi, metabolic engineering, primary metabolites, secondary metabolites, flux balance analysis

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