Decode and rewire: programming Komagataella phaffii for bioproduction with synthetic transcriptional tools

Wei X., Cong W., Zhou H., Zhang J., ÇALIK P.

Trends in Biotechnology, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Review
  • Publication Date: 2026
  • Doi Number: 10.1016/j.tibtech.2025.12.009
  • Journal Name: Trends in Biotechnology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Compendex, EMBASE, Environment Index, MEDLINE
  • Keywords: Komagataella phaffii, reverse-engineering TME interactions, sustainable carbon sources, synthetic promoter, transcription factor, transcriptional machinery elements (TMEs)
  • Middle East Technical University Affiliated: Yes

Abstract

The yeast Komagataella phaffii is a leading producer of secreted therapeutic and industrial proteins. Its excellent traits make it a primary host for the production of value-added carbon compounds, including native metabolites, heterologous biomolecules, and synthetic chemicals. Recent breakthrough discoveries in engineering synthetic promoters have set the stage for novel bioprocesses that utilize sustainable carbon sources through directed evolution methods, ushering in a new era in bioindustry. This review discusses how engineering-directed transcriptional machinery element (TME) interaction-driven methodologies can unlock latent potential to rewire expression for the directed evolution of metabolic functions. We highlight discoveries in the design of transcriptional switches and metabolic switches, the reverse-engineering TME interaction via synthetic transcription factors, forcing K. phaffii for directed evolution.