Plasmid-Based Gene Knockout Strategy with Subsequent Marker Recycling in Pichia pastoris

Methods Mol Biol. 2022:2513:135-151. doi: 10.1007/978-1-0716-2399-2_9.

Abstract

Gene knockout is a key technology in the development of cell factories and basic research alike. The methylotrophic yeast Pichia pastoris is typically employed as a producer of proteins and of fine chemicals, due to its ability to accumulate high cell densities in conjunction with a set of strong inducible promoters. However, protocols for genome engineering in this host are still cumbersome and time-consuming. Moreover, extensive genome engineering raises the need for a multitude of selection markers, which are limited in P. pastoris. In this chapter, we describe a fast and efficient method for gene disruption in P. pastoris that utilizes marker recycling to enable repetitive genome engineering cycles. A set of ready-to-use knockout vectors simplifies cloning procedures and facilitates quick knockout generation.

Keywords: Gene disruption; Homologous recombination; Knockout plasmids; Marker recycling; Pichia pastoris.

MeSH terms

  • Biomarkers
  • Gene Knockout Techniques
  • Plasmids / genetics
  • Saccharomyces cerevisiae
  • Saccharomycetales*

Substances

  • Biomarkers

Supplementary concepts

  • Komagataella pastoris