"Fight-flight-or-freeze" - how Yarrowia lipolytica responds to stress at molecular level?

Abstract

Yarrowia lipolytica is a popular yeast species employed in multiple biotechnological production processes. High resistance to extreme environmental conditions or metabolic burden triggered by synthetically forced over-synthesis of a target metabolite has its practical consequences. The proud status of an "industrial workhorse" that Y. lipolytica has gained is directly related to such a quality of this species. With the increasing amount of knowledge coming from detailed functional studies and comprehensive omics analyses, it is now possible to start painting the landscape of the molecular background behind stress response and adaptation in Y. lipolytica. This review summarizes the current state-of-art of a global effort in revealing how Y. lipolytica responds to both environmental threats and the intrinsic burden caused by the overproduction of recombinant secretory proteins at the molecular level. Detailed lists of genes, proteins, molecules, and biological processes deregulated upon exposure to external stress factors or affected by over-synthesis of heterologous proteins are provided. Specificities and universalities of Y. lipolytica cellular response to different extrinsic and intrinsic threats are highlighted. KEY POINTS: • Y. lipolytica as an industrial workhorse is subjected to multiple stress factors. • Cellular responses together with involved genes, proteins, and molecules are reviewed. • Native stress response mechanisms are studied and inspire engineering strategies.

Keywords: Environmental stress; Heterologous protein; Metabolic burden; Recombinant protein secretion; Stress response; Yeast.

Fig. 1

Schematic representation of processes involved in general stress-response in Y. lipolytica. Highlighted biological processes: structural and compositional changes to the cell membrane, loss of cell integrity; structural and compositional changes to cell wall – formation of protruding elements, enhanced formation of extracellular vesicles; cell membrane invagination hallmarking qualitative and quantitative modifications of channels and sensor/changes to cell size; enrichment of biological processes localized to cell surface hallmark possible dimorphic transition; oxidative degradation of lipids, proteins, and DNA; ubiquitination, proteasomal degradation, and vacuolar lysis of proteins; mitochondria over-loading and outburst of the oxidative stress response; chromatin structure modifications and changes to genes expression/protein abundance profiles; activation of membrane transporters and ion pumps