title: The tip and hidden part of the iceberg: Proteinogenic and non-proteinogenic aliphatic amino acids.
abstract: Amino acids are the essential building blocks of proteins and, therefore, living organisms. While the focus often lies on the canonical or proteinogenic amino acids, there is also a large number of non-canonical amino acids to explore. Some of them are part of toxins or antibiotics in fungi, bacteria or animals (e.g. sponges). Some others operate at the translational level like an "undercover agent".
  
  
  
  Here we give an overview of natural aliphatic amino acids, up to a side chain length of five carbons, without rings and with an unmodified backbone, and have a closer look on each of them. Some of them are dehydro amino acids with double or even triple bonds. Moreover, we outline mathematical methods for enumerating the complete list of all potential aliphatic amino acids of a given chain length. This should be of interest for synthetic biology.
  
  
  
  Most non-proteinogenic amino acids are found within fungi, with particularly many produced by Amanita species as defence chemicals. Several are incorporated into peptide antibiotics. Some of the amino acids occur due to broad substrate specificity of the branched-chain amino acid synthesis pathways. A large variety of amino acids were also found in the Murchison meteorite.
  
  
  
  Non-proteinogenic amino acids are of interest for numerous medical applications: discovery of new antibiotics, support in designing synthetic antibiotics, improvement of protein and peptide pharmaceuticals by avoiding incorporation of non-canonical amino acids, study of toxic cyanobacteria and other applications.
authors.affiliation: Dept. of Bioinformatics, University of Jena, Ernst-Abbe-Pl. 2, 07743 Jena, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Fichtner
authors.affiliation: Dept. of Microbiology and Molecular Biology, University of Jena, Neugasse 25, D-07743 Jena, Germany; Jena Microbial Resource Collection (JMRC), Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute Jena, Beutenbergstrasse 11a, D-07745 Jena, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Voigt
authors.affiliation: Dept. of Bioinformatics, University of Jena, Ernst-Abbe-Pl. 2, 07743 Jena, Germany. Electronic address: stefan.schu@uni-jena.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schuster
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D011506:Proteins
keywords: Aliphatic amino acids; Chemical combinatorics; Dehydro amino acids; Fungal secondary metabolites; Peptide antibiotics; Toxic peptides