Role of the Extremolytes Ectoine and Hydroxyectoine as Stress Protectants and Nutrients: Genetics, Phylogenomics, Biochemistry, and Structural Analysis

Abstract

Fluctuations in environmental osmolarity are ubiquitous stress factors in many natural habitats of microorganisms, as they inevitably trigger osmotically instigated fluxes of water across the semi-permeable cytoplasmic membrane. Under hyperosmotic conditions, many microorganisms fend off the detrimental effects of water efflux and the ensuing dehydration of the cytoplasm and drop in turgor through the accumulation of a restricted class of organic osmolytes, the compatible solutes. Ectoine and its derivative 5-hydroxyectoine are prominent members of these compounds and are synthesized widely by members of the Bacteria and a few Archaea and Eukarya in response to high salinity/osmolarity and/or growth temperature extremes. Ectoines have excellent function-preserving properties, attributes that have led to their description as chemical chaperones and fostered the development of an industrial-scale biotechnological production process for their exploitation in biotechnology, skin care, and medicine. We review, here, the current knowledge on the biochemistry of the ectoine/hydroxyectoine biosynthetic enzymes and the available crystal structures of some of them, explore the genetics of the underlying biosynthetic genes and their transcriptional regulation, and present an extensive phylogenomic analysis of the ectoine/hydroxyectoine biosynthetic genes. In addition, we address the biochemistry, phylogenomics, and genetic regulation for the alternative use of ectoines as nutrients.

Metabolic Engineering of Corynebacterium glutamicum for High‐Level Ectoine Production: Design, Combinatorial Assembly, and Implementation of a Transcriptionally Balanced Heterologous Ectoine Pathway

“…In this study, C. glutamicum , a well‐established industrial microbe, was upgraded for the production of ectoine from sugar and molasses. From an industrial perspective, ectoine is a high‐priced molecule (€900 kg −1 ) with a rather small market volume . This market situation prioritizes the key indicators for economic performance in the order titer > productivity > yield.…”

“…Various microbes accumulate ectoine (1,4,5,6‐tetrahydro‐2‐methyl‐4‐pyrimidine‐carboxylic acid) as a protective extremolyte under conditions of environmental stress, e.g., high osmolarity, dryness, and extreme temperature . The chemical is of recognized commercial value because of its remarkable ability to protect macromolecules, cells, and tissues . Its current sales price is approximately US$1000 kg −1 , making ectoine a high‐priced product .…”

“…The chemical is of recognized commercial value because of its remarkable ability to protect macromolecules, cells, and tissues . Its current sales price is approximately US$1000 kg −1 , making ectoine a high‐priced product . The applications of ectoine are manifold and include skin preservation, skin protection against cell damage and aging, and the treatment of diseases such as atopic dermatitis, lung inflammation, allergic rhinitis, and Alzheimer's disease .…”

The MocR‐like transcription factors: pyridoxal 5′‐phosphate‐dependent regulators of bacterial metabolism

“…MocR‐TFs have been found to control several different metabolic processes that involve vitamin B 6 and amino acids, which are canonical ligands of PLP‐dependent enzymes. However, MocR‐TFs are also implicated in the metabolism of compounds that are not directly related to the classical substrates of PLP‐dependent enzymes, such as rhizopine, an opine‐like compound that is structurally similar to an amino sugar, and ectoine, a protectant against osmotic challenges and extremes in both low and high growth temperatures .…”

“…not directly related to the classical substrates of PLPdependent enzymes, such as rhizopine, an opine-like compound that is structurally similar to an amino sugar, and ectoine, a protectant against osmotic challenges and extremes in both low and high growth temperatures [17].…”