Effects of codon optimization on the mRNA levels of heterologous genes in filamentous fungi

Mizuki Tanaka, Masafumi Tokuoka, Katsuya Gomi

Research output: Contribution to journalShort surveypeer-review

16 Citations (Scopus)

Abstract

Filamentous fungi, particularly Aspergillus species, have recently attracted attention as host organisms for recombinant protein production. Because the secretory yields of heterologous proteins are generally low compared with those of homologous proteins or proteins from closely related fungal species, several strategies to produce substantial amounts of recombinant proteins have been conducted. Codon optimization is a powerful tool for improving the production levels of heterologous proteins. Although codon optimization is generally believed to improve the translation efficiency of heterologous genes without affecting their mRNA levels, several studies have indicated that codon optimization causes an increase in the steady-state mRNA levels of heterologous genes in filamentous fungi. However, the mechanism that determines the low mRNA levels when native heterologous genes are expressed was poorly understood. We recently showed that the transcripts of heterologous genes are polyadenylated prematurely within the coding region and that the heterologous gene transcripts can be stabilized significantly by codon optimization, which is probably attributable to the prevention of premature polyadenylation in Aspergillus oryzae. In this review, we describe the detailed mechanism of premature polyadenylation and the rapid degradation of mRNA transcripts derived from heterologous genes in filamentous fungi.

Original languageEnglish
Pages (from-to)3859-3867
Number of pages9
JournalApplied Microbiology and Biotechnology
Volume98
Issue number9
DOIs
Publication statusPublished - 2014 May

Keywords

  • 3′-end processing signal
  • Codon optimization
  • Filamentous fungi
  • Heterologous protein production
  • Polyadenylation site
  • Steady-state mRNA level

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

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