Archaea as a Model System for Molecular Biology and Biotechnology

Abstract

Archaea represents the third domain of life, displaying a closer relationship with eukaryotes than bacteria. These microorganisms are valuable model systems for molecular biology and biotechnology. In fact, nowadays, methanogens, halophiles, thermophilic euryarchaeota, and crenarchaeota are the four groups of archaea for which genetic systems have been well established, making them suitable as model systems and allowing for the increasing study of archaeal genes’ functions. Furthermore, thermophiles are used to explore several aspects of archaeal biology, such as stress responses, DNA replication and repair, transcription, translation and its regulation mechanisms, CRISPR systems, and carbon and energy metabolism. Extremophilic archaea also represent a valuable source of new biomolecules for biological and biotechnological applications, and there is growing interest in the development of engineered strains. In this review, we report on some of the most important aspects of the use of archaea as a model system for genetic evolution, the development of genetic tools, and their application for the elucidation of the basal molecular mechanisms in this domain of life. Furthermore, an overview on the discovery of new enzymes of biotechnological interest from archaea thriving in extreme environments is reported.

Teaching old dogs new tricks: genetic engineering methanogens

“…Homologous recombination is a natural cellular process that exchanges the genetic material between two DNA molecules that have similar (i.e., homologous) sequences, and is used for genetic repair and recombination. Although homologous recombination allows for precise targeted gene editing, in some cases, genomic integration can require a long homology arm, which increases the genetic construct length and decreases the likelihood that the cell will successfully uptake the construct ( 77 , 104 , 105 ).…”

Rational design of unrestricted pRN1 derivatives and their application in the construction of a dual plasmid vector system for Saccharolobus islandicus

“…These archaea are probably ancestors of eukaryotes, since they share hundreds of proteins involved in cellular processes such as membrane trafficking with eukaryotes 7 , 8 , 9 . Therefore, archaeal models are important not only for the investigation of novel biological principles in their own rights but also for exploring the origin of eukaryotes and the evolution of eukaryotic biological features 5 , 10 , 11 .…”

5’-untranslated region sequences enhance plasmid-based protein production inSulfolobus acidocaldarius

“…Most commonly, yeast or bacteria are used for gene overexpression, with Escherichia coli standing out as the most commonly used bacterial expression host (Rosano & Ceccarelli, 2014). Despite continuous advancements in expression systems, challenges such as suboptimal codon usage and posttranslational modifications, protein misfolding, and the formation of insoluble aggregates persist, hindering successful gene overexpression (de Lise et al, 2023).…”

“…With its established genetic system and genomic stability, the thermoacidophilic, aerobic archaeon Sulfolobus acidocaldarius (T opt 70 - 75°C, pH opt 2 - 3; Brock et al, 1972; Chen et al, 2005) offers a versatile platform for gene deletion studies and overexpression (de Lise et al, 2023, Wagner et al, 2012; Lewis et al, 2021). Inducible expression vectors utilizing sugar-inducible promoters (e.g.…”