Insights into the structural basis of substrate recognition by histidinol-phosphate aminotransferase from<i>Corynebacterium glutamicum</i>

Marienhagen, Jan; Sandalova, T.; Sahm, Hermann; Eggeling, Lothar; Schneider, Günter

doi:10.1107/s0907444908009438

Cited by 8 publications

(23 citation statements)

References 25 publications

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“…The enzyme exhibits a K m value for Hol‐P of 0.89 ± 0.1 mM, a k cat value of 1.18 ± 0.1 s −1 and a specific activity of 2.8 μmol min −1 mg −1 (Marienhagen et al ., ). Interestingly, HisC Cg shows also activity with the precursors of leucine and aromatic amino acids in in vitro assays, but the K m values are two orders of magnitude higher compared with those observed with the histidine precursor and HisC Cg does not contribute to aromatic amino acid synthesis in vivo (Marienhagen et al ., 2005; 2008). The crystal structure of HisC Cg has been solved revealing a three‐domain structure of the monomer, with a N‐terminal arm, a large PLP binding domain, and a small C‐terminal domain (Marienhagen et al ., ).…”

Section: Enzymes Involved In Histidine Biosynthesismentioning

confidence: 97%

“…Interestingly, HisC Cg shows also activity with the precursors of leucine and aromatic amino acids in in vitro assays, but the K m values are two orders of magnitude higher compared with those observed with the histidine precursor and HisC Cg does not contribute to aromatic amino acid synthesis in vivo (Marienhagen et al ., 2005; 2008). The crystal structure of HisC Cg has been solved revealing a three‐domain structure of the monomer, with a N‐terminal arm, a large PLP binding domain, and a small C‐terminal domain (Marienhagen et al ., ). HisC Cg dimerization occurs via extensive hydrophobic interactions and 24 intersubunit hydrogen bonds with the N‐terminal arm contributing significantly to the intersubunit interface (Marienhagen et al ., ).…”

Section: Enzymes Involved In Histidine Biosynthesismentioning

confidence: 99%

“…The seventh step of histidine biosynthesis is the transamination of IAP to L-histidinol phosphate (Hol-P) using glutamate as amino group donor (Alifano et al, 1996). This step is catalysed by the pyridoxal 5′-phosphate (PLP) dependent histidinol-phosphate aminotransferase in C. glutamicum (Marienhagen et al, 2008). Like HisC from E. coli and S. typhimurium (Winkler, 1996), native HisCCg acts as a dimer (Marienhagen et al, 2008).…”

Section: Histidinol-phosphate Aminotransferase (Hisc)mentioning

confidence: 99%

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Histidine biosynthesis, its regulation and biotechnological application in Corynebacterium glutamicum

Kulis-Horn

Persicke

Kalinowski

2013

Microbial Biotechnology

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l-Histidine biosynthesis is an ancient metabolic pathway present in bacteria, archaea, lower eukaryotes, and plants. For decades l-histidine biosynthesis has been studied mainly in Escherichia coli and Salmonella typhimurium, revealing fundamental regulatory processes in bacteria. Furthermore, in the last 15 years this pathway has been also investigated intensively in the industrial amino acid-producing bacterium Corynebacterium glutamicum, revealing similarities to E. coli and S. typhimurium, as well as differences. This review summarizes the current knowledge of l-histidine biosynthesis in C. glutamicum. The genes involved and corresponding enzymes are described, in particular focusing on the imidazoleglycerol-phosphate synthase (HisFH) and the histidinol-phosphate phosphatase (HisN). The transcriptional organization of his genes in C. glutamicum is also reported, including the four histidine operons and their promoters. Knowledge of transcriptional regulation during stringent response and by histidine itself is summarized and a translational regulation mechanism is discussed, as well as clues about a histidine transport system. Finally, we discuss the potential of using this knowledge to create or improve C. glutamicum strains for the industrial l-histidine production.

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Section: Enzymes Involved In Histidine Biosynthesismentioning

confidence: 97%

Section: Enzymes Involved In Histidine Biosynthesismentioning

confidence: 99%

Section: Histidinol-phosphate Aminotransferase (Hisc)mentioning

confidence: 99%

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Histidine biosynthesis, its regulation and biotechnological application in Corynebacterium glutamicum

Kulis-Horn

Persicke

Kalinowski

2013

Microbial Biotechnology

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“…Here, the in vivo function could be studied only when the other two genes were inactivated (8). Nonetheless, we succeeded in identifying the function of 11 ATs of 20 putative PLP-dependent proteins encoded in the Corynebacterium glutamicum genome, thus gaining a global view of the transamination activities in this bacterium (16,17). This bacterium is of particular interest due to its excellent amino acid production properties.…”

mentioning

confidence: 99%

Metabolic Function of Corynebacterium glutamicum Aminotransferases AlaT and AvtA and Impact on l -Valine Production

Marienhagen

Eggeling

2008

Appl Environ Microbiol

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Aminotransferases (ATs) interacting with L-alanine are the least studied bacterial ATs. Whereas AlaT converts pyruvate to L-alanine in a glutamate-dependent reaction, AvtA is able to convert pyruvate to L-alanine in an L-valine-dependent manner. We show here that the wild type of Corynebacterium glutamicum with a deletion of either of the corresponding genes does not exhibit an explicit growth deficiency. However, a double mutant was auxotrophic for L-alanine, showing that both ATs can provide L-alanine and that they are the only ATs involved. Kinetic studies with isolated enzymes demonstrate that the catalytic efficiency, k cat /K m , of AlaT is higher than 1 order of magnitude in the direction of L-alanine formation (3.5 ؋ 10 4 M ؊1 s ؊1 ), but no preference was apparent for AvtA, suggesting that AlaT is the principal L-alanine-supplying enzyme. This is in line with the cytosolic L-alanine concentration, which is reduced in the exponential growth phase from 95 mM to 18 mM by a deletion of alaT, whereas avtA deletion decreases the L-alanine concentration only to 76 mM. The combined data show that the presence of both ATs has subtle but obvious consequences on balancing intracellular amino acid pools in the wild type. The consequences are more obvious in an L-valine production strain where a high intracellular drain-off of the L-alanine precursor pyruvate prevails. We therefore used deletion of alaT to successfully reduce the contaminating L-alanine in extracellular accumulated L-valine by 80%.Among the numerous transformations of amino acids performed by pyridoxal-5Ј-phosphate (PLP)-dependent enzymes, the reversible transfer of amino groups from the amino acids to 2-oxo-acids is predominant. Such reactions are catalyzed by aminotransferases (ATs), which play a vital role in the synthesis of amino acids as well as in amino acid interconversions (5).A functional study of ATs in a single organism may encounter problems due to the large number of ATs usually present, their closely related structure, and overlapping substrate specificities (10,19). This is evident, for instance, for Escherichia coli and its three ATs encoded by tyrB, aspC, and ilvE, which are involved in the synthesis of aromatic amino acids. Here, the in vivo function could be studied only when the other two genes were inactivated (8). Nonetheless, we succeeded in identifying the function of 11 ATs of 20 putative PLP-dependent proteins encoded in the Corynebacterium glutamicum genome, thus gaining a global view of the transamination activities in this bacterium (16,17). This bacterium is of particular interest due to its excellent amino acid production properties. Currently, most of the 2 ϫ 10 6 tons of amino acids produced per year are synthesized by fermentation with C. glutamicum (13), and a recent monograph discusses a number of features of this useful bacterium (6).Among the amino acids made with C. glutamicum are L-isoleucine and L-valine, which are mostly used for pharmaceutical purposes and therefore are required to have the highest purity....

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“…2A-2D) the enzymes of class I, II, IV and V can be defined as -transaminases in that they transfer the amino group to and from the position to a carboxylic acid (or phosphate ester in the case of the class II enzyme L-histidinol-phosphate transaminase [44]). A recent addition to the class II enzymes (based on the protein amino acid sequence alignment) is from the bacterium Mezorhizobium sp.…”

Section: Alpha Transaminasesmentioning

confidence: 99%

High-Yield Biocatalytic Amination Reactions in Organic Synthesis

Ward¹,

Wohlgemuth²

2010

COC

140

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The amino functionality gives important biological activity in pharmaceutical compounds. The formation of chiral amines and amino acids can be accomplished by several chemical routes but enzymatic formation of amines offers many advantages in preparing chiral amino compounds or amination of fragile compounds compared to stoichiometric or catalytic chemical transformations. Biocatalytic routes to amines primarily use enzymes of the transaminase class (also known as aminotransferases) which transfer the amino function from a donor organic compound to a ketone or aldehyde acceptor. Although known since 1937, the transamination reaction experiences renewed interest due to the advances in biochemistry and molecular biology and the excellent selectivity of biocatalysts. Other enzymes that have been used to synthesize chiral amines are from the phenylalanine ammonia lyase class that use ammonia as the amino source. The use of recombinant enzymes for the biocatalytic preparation of amines is expanding at a great rate and the range of enzymes revealed in DNA sequence databases is of the order of tens of thousands. Since a large number of substrates like ketones, hydroxyketones and ketoacids can be made by chemical synthesis, the growing toolbox of -, -, -, -, -and -transaminases enable the synthesis of various new chemical entities by biocatalytic amination reactions. In order to simplify the isolation and purification of the product, it is useful to drive the amination reaction to completion. The biocatalytic processes that have been developed show different strategies of overcoming the kinetic limitations of the transaminase reactions and show how some enzymes have been used in processes to make large quantities of chiral compounds with amino functionalities.

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Insights into the structural basis of substrate recognition by histidinol-phosphate aminotransferase fromCorynebacterium glutamicum

Cited by 8 publications

References 25 publications

Histidine biosynthesis, its regulation and biotechnological application in Corynebacterium glutamicum

Histidine biosynthesis, its regulation and biotechnological application in Corynebacterium glutamicum

Metabolic Function of Corynebacterium glutamicum Aminotransferases AlaT and AvtA and Impact on l -Valine Production

High-Yield Biocatalytic Amination Reactions in Organic Synthesis

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