Non-proteinogenic amino acids

Non-proteinogenic amino acids are amino acids that are not incorporated into proteins during translation . They therefore often act as amino acid antagonists in the amino acid metabolism and protein biosynthesis . The amino hetero oxo acids are to be distinguished from the aminocarboxylic acids . Further distinguishing criteria are the stability ( isomerism ) of the amino group relative to the acid group and, if applicable, the configuration of these functional groups, especially in α-amino acids.

properties

Akee plant with fruit. The unripe seed coat contains the non-proteinogenic amino acid hypoglycine .

Structural formula of hypoglycine - a non-proteinogenic amino acid.

To date, over 400 non-proteinogenic amino acids are known to be found in organisms. These naturally formed, non-proteinogenic amino acids fulfill various functions. Some arise as post-translational modifications in proteins (e.g. phosphotyrosine , hydroxyproline , formylmethionine , cystine , lanthionine , djenkolic acid , 2,6-diaminopimelic acid ). Others are metabolites in the metabolism (e.g. ornithine , citrulline , argininosuccinate , sarcosine , homoserine , homocysteine , L-DOPA , 5-hydroxytryptophan ). Others serve as hormones ( L - thyroxine ) and neurotransmitters (e.g. GABA , D - serine ) or as toxins ( β-methylamino-alanine , ibotenic acid , L - azetidine-2-carboxylic acid ).

Over 250 different non-proteinogenic amino acids have been found to be the building blocks of oligopeptides or short polypeptides, which are built up by non- ribosomal peptide synthetases from various types of archaea , bacteria , fungi and nudibranchs .

Artificially produced amino acids are z. B. the inhibitors isoserine , 2-amino-5-phosphonovaleric acid and the synthesis base for β-lactam antibiotics D- phenylglycine . In the Miller-Urey experiment , among other things, the amino acids norvaline and norleucine were artificially produced.

structure

In contrast to the proteinogenic amino acids, not all non-proteinogenic amino acids are L-α-amino acids, e.g. B. the group of D-amino acids or the non-α-amino acids such as β-alanine , GABA, δ-aminolevulinic acid or 4-aminobenzoic acid . Other non-proteinogenic amino acids have a modified peptide backbone such as 3-aminoisobutyric acid or dehydroalanine . There are also non-proteinogenic amino acids with two centers of chirality such as e.g. B. cystathionine , lanthionine, djenkolic acid or 2,6-diaminopimelic acid. Sulfur- containing non-proteinogenic amino acids are e.g. B. homocysteine , ethionine and felinine . Selenium- containing non-proteinogenic amino acids are methyl selenocysteine and selenomethionine .

Some non-proteinogenic amino acids

amino acid	function	structure	Structural formula
Taurine
L - thyroxine (T 4 )	Hormone the thyroid	L-α-amino acid
2,6-diaminopimelic acid (DAP)	Component in bacterial cell walls	α-amino acid with 2 stereocenters
Azetidine-2-carboxylic acid	Toxin of the lily of the valley	L-α-amino acid, secondary amine in a ring
Sarcosine	Metabolic intermediate in amino acid metabolism	N -methyl-α-amino acid
Homoser	Methionine breakdown product	L-α-amino acid
Lanthionine	in structural proteins	α-amino acid with 2 stereocenters
Djenkolic acid	Food poison from Archidendron jiringa (Jengkol), a legume	α-amino acid with 2 stereocenters
Cystathionine	Intermediate in the biosynthesis of cysteine	α-amino acid with 2 stereocenters
L - homocysteine	Methionine breakdown product	L-α-amino acid
Ethionine	Methionine - Antagonist	L-α-amino acid
5-aminolevulinic acid (5-ALA)	Preliminary stage of heme	δ-amino acid
p-aminobenzoic acid (PABA)	bacterial folic acid synthesis	aromatic backbone
Dehydroalanine (DHA)	Cysteine breakdown product	Double bond on the α-C atom
γ-aminobutyric acid (GABA)	inhibitory neurotransmitter	γ-amino acid
3-aminoisobutyric acid	is involved in lipid metabolism	β-amino acid
L - ornithine	Metabolic intermediate in the urea cycle	L-α-amino acid
L - citrulline	Metabolic intermediate in the urea cycle	L-α-amino acid
Argininosuccinate	Metabolic intermediate in the urea cycle	L-α-amino acid
L - 3,4-dihydroxyphenylalanine ( L -DOPA)	Metabolic intermediate in the synthesis of catecholamines	L-α-amino acid
L - 5-Hydroxytryptophan (5-HTP)	Metabolic intermediate in serotonin synthesis	L-α-amino acid
β-alanine	Building block of coenzyme A	β-amino acid
β-N-methylamino-alanine	Neurotoxin in cyanobacteria	L-α-amino acid
Ibotenic acid	Mushroom poison	L-α-amino acid
D - valine	Part of the antibiotic valinomycin	D-amino acid
D - alanine	Component in bacterial cell walls	D-amino acid
D - glutamic acid	Component in bacterial cell walls	D-amino acid
Hypoglycine	Akee plant toxin	L-α-amino acid
L -4- hydroxyproline	Stabilizes the structure of the collagen	L-α-amino acid, secondary amine in a ring
Pipecolic acid	Lysine breakdown product	L-α-amino acid, secondary amine in a ring

Applications

Non-proteinogenic amino acids can be incorporated into proteins by non- ribosomal peptide synthetases , by protein ligation , by peptide synthesis or by genetic reprogramming. With peptides containing non-proteinogenic amino acids, the substrate specificities of peptidases can be investigated and protease inhibitors developed. β-peptides are made up of β-amino acids.

Individual evidence

1. ^ Jan Koolman, Klaus Heinrich Roehm: Color Atlas of Biochemistry . 3rd edition, Thieme 2012. ISBN 978-3-13-169693-9 .
2. ^ Gerhard Habermehl, Peter E. Hammann: Naturstoffchemie: An introduction . Springer-Verlag, 2013, ISBN 978-3-662-08929-3 ( Google Books ).
3. ^ Peter Nuhn: Naturstoffchemie , S. Hirzel Wissenschaftliche Verlagsgesellschaft Stuttgart 1990, ISBN 3-7776-0473-9 . P. 70.
4. ↑ see entries monomers in the NORINE database .
5. ↑ GH Hur, CR Vickery, MD Burkart: Explorations of catalytic domains in non-ribosomal peptide synthetase enzymology. In: Natural product reports. Volume 29, Number 10, October 2012, pp. 1074-1098, doi : 10.1039 / c2np20025b , PMID 22802156 .
6. ^ U. Arnold: Incorporation of non-natural modules into proteins: structural features beyond the genetic code. In: Biotechnology letters. Volume 31, Number 8, August 2009, pp. 1129-1139, doi : 10.1007 / s10529-009-0002-9 , PMID 19404746 .
7. ↑ A. Ohta, Y. Yamagishi, H. Suga: Synthesis of biopolymers using genetic code reprogramming. In: Current opinion in chemical biology. Volume 12, Number 2, April 2008, pp. 159-167, doi : 10.1016 / j.cbpa.2007.12.009 , PMID 18249198 .
8. ^ Y. Lu, S. Freeland: On the evolution of the standard amino-acid alphabet. In: Genome biology. Volume 7, number 1, 2006, p. 102, doi : 10.1186 / gb-2006-7-1-102 , PMID 16515719 , PMC 1431706 (free full text).
9. ↑ P. Kasperkiewicz, AD Gajda, M. Drąg: Current and prospective applications of non-proteinogenic amino acids in profiling of proteases substrate specificity. In: Biological chemistry. Volume 393, number 9, September 2012, pp. 843-851, doi : 10.1515 / hsz-2012-0167 , PMID 22944686 .