Heterologous Gene Expression in Filamentous Fungi

Xiaoyun Su, George Schmitz, Meiling Zhang, Roderick I. Mackie, Isaac K.O. Cann

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Filamentous fungi are critical to production of many commercial enzymes and organic compounds. Fungal-based systems have several advantages over bacterial-based systems for protein production because high-level secretion of enzymes is a common trait of their decomposer lifestyle. Furthermore, in the large-scale production of recombinant proteins of eukaryotic origin, the filamentous fungi become the vehicle of choice due to critical processes shared in gene expression with other eukaryotic organisms. The complexity and relative dearth of understanding of the physiology of filamentous fungi, compared to bacteria, have hindered rapid development of these organisms as highly efficient factories for the production of heterologous proteins. In this review, we highlight several of the known benefits and challenges in using filamentous fungi (particularly Aspergillus spp., Trichoderma reesei, and Neurospora crassa) for the production of proteins, especially heterologous, nonfungal enzymes. We review various techniques commonly employed in recombinant protein production in the filamentous fungi, including transformation methods, selection of gene regulatory elements such as promoters, protein secretion factors such as the signal peptide, and optimization of coding sequence. We provide insights into current models of host genomic defenses such as repeat-induced point mutation and quelling. Furthermore, we examine the regulatory effects of transcript sequences, including introns and untranslated regions, pre-mRNA (messenger RNA) processing, transcript transport, and mRNA stability. We anticipate that this review will become a resource for researchers who aim at advancing the use of these fascinating organisms as protein production factories, for both academic and industrial purposes, and also for scientists with general interest in the biology of the filamentous fungi.

Original languageEnglish (US)
Title of host publicationAdvances in Applied Microbiology
PublisherAcademic Press Inc.
Pages1-61
Number of pages61
DOIs
StatePublished - 2012

Publication series

NameAdvances in Applied Microbiology
Volume81
ISSN (Print)0065-2164

Keywords

  • Aspergillus nidulans
  • Aspergillus niger
  • Filamentous fungi
  • Gene expression
  • Heterologous
  • Neurospora crassa
  • Protein secretion
  • RNA interference
  • Repeat-induced point mutation
  • Trichoderma reesei

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology

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