5

Microbiology Monographs
Series Editor: Alexander Steinbchel

Microbiology Monographs
Volumes published in the series

Inclusions in Prokaryotes
Jessup M. Shively (Editor)
Volume 1 (2006)
Complex Intracellular Structures in Prokaryotes
Jessup M. Shively (Editor)
Volume 2 (2006)
Magnetoreception and Magnetosomes in Bacteria
Dirk Schler (Editor)
Volume 3 (2007)
Predatory Prokaryotes Biology, Ecology and Evolution
Edouard Jurkevitch (Editor)
Volume 4 (2007)

Amino Acid Biosynthesis

Pathways, Regulation
and Metabolic Engineering
Volume Editor: Volker F. Wendisch

With 64 Figures, 6 in Color

123

Volume Editor:
Prof. Dr. Volker F. Wendisch
Institute of Molecular Microbiology and Biotechnology
Westfalian Wilhelms University Mnster
Corrensstr. 3
48149 Mnster
Germany
e-mail: wendisch@uni-muenster.de
Series Editor:
Professor Dr. Alexander Steinbchel
Institut fr Molekulare Mikrobiologie und Biotechnologie
Westflische Wilhelms-Universitt
Corrensstrae 3
48149 Mnster
Germany
e-mail: steinbu@uni-muenster.de

Library of Congress Control Number: 2006940356

ISSN 1862-5576
ISBN 978-3-540-48595-7 Springer Berlin Heidelberg New York
DOI 10.1007/978-3-540-48596-4

This work is subject to copyright. All rights are reserved, whether the whole or part of the material
is concerned, specically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microlm or in any other way, and storage in data banks. Duplication of
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c Springer-Verlag Berlin Heidelberg 2007


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and therefore free for general use.
Editor: Dr. Christina Eckey, Heidelberg, Germany
Desk Editor: Dr. Jutta Lindenborn, Heidelberg, Germany
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Preface

Amino acids are simple organic compounds containing at least one amino
and one carboxylic function. The L--amino acids and glycine can be considered building blocks of life since they constitute the biopolymers proteins
in all organisms, but also D-isomers, e.g. D-alanine in bacterial cell walls,
and - and -amino acids like -alanine as component of vitamin B5 and
-aminobutyrate as neurotransmitter occur in nature. While mature proteins
contain many different amino acids due to post-translational modications,
only 22 proteinogenic L--amino acids are genetically encoded, i.e. they are
used for protein biosynthesis as amino acyl-tRNAs by the ribosome. Since
the deciphering of the genetic code for 20 amino acids about 40 years ago,
L-selenocysteine (Chambers et al. 1986; Zinoni et al. 1986) and L-pyrrolysine
(Hao et al. 2002; Srinivasan et al. 2002) were discovered as the 21st and 22nd
genetically encoded amino acids. The co-translational insertion of selenocysteine and pyrrolysine into nascent proteins requires unique cis- and transacting factors to recode UGA and UAG stop codons, respectively, as codons for
selenocysteine and pyrrolysine, respectively. The existence of further widely
distributed and genetically encoded amino acids is unlikely as suggested in
a recent bioinformatic analysis of tRNAs encoded in about 150 bacterial and archaeal genomes (Lobanov et al. 2006). The essential L-amino acids isoleucine,
leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine
cannot be synthesized by humans, but have to supplied in the diet, and infants
require arginine and histidine in addition. Microorganisms differ considerably
in their capabilities to synthesize amino acids de novo, for example Leuconostoc mesenteroides only grows, when 16 amino acids are supplied, while bacteria
like Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum are able
to synthesize all amino acids de novo from ammonium.
This monograph deals with amino acid biosynthetic pathways and their
genetic and biochemical regulation on one hand and with the use and metabolic
engineering of microorganisms for biotechnological production of amino acids
on the other. The current knowledge of amino acid metabolic pathways and
transport systems specic for uptake or export of amino acids is covered.
The characterization of the control mechanisms of amino acid biosynthesis
have revealed fundamental insights into genetic and biochemical regulation.
Feedback inhibition of biosynthetic enzymes by metabolic end-products (e.g.

VI

Preface

of aspartate transcarbamoylase in the biosynthesis of arginine and pyrimidines

by CTP), enzyme activity control by covalent modication (e.g. adenylation
of glutamine synthetase), co-repressor dependent transcriptional repression
(e.g. by the tryptophan-activated repressor of the trp operon), and attenuation control (e.g. translation-mediated attenuation of the tryptophan biosynthetic operon) are integral parts of biochemistry, genetics and microbiology
textbooks. Recently, global gene expression analyses allowed determining the
regulons of a number of transcriptional regulators of amino acid biosynthesis.
Moreover, the discovery of a lysine-specic riboswitch (Sudarsan et al. 2003),
a new class of regulatory elements, illustrates that the characterization of the
regulation of amino acid metabolism continues to spur new discoveries.
Amino acids are used on the basis of their chemical characteristics, physiological activities, nutritional value and taste as chemical building blocks, as
pharmaceuticals and, particularly, as food and feed additives. The discovery of
C. glutamicum as suitable catalyst to produce the avor enhancer monosodium
glutamate 1957 in Japan marked the birth of the amino acid fermentation industry. Reports on the beginnings of microbial amino acid production (Yamada
et al. 1972; Aida et al. 1986; Enei et al. 1989) and an up-to-date review of C.
glutamicum (Eggeling & Bott 2005) are available. In this monograph, recent
achievements to enable or to improve production of amino acids and of dipeptides by fermentation and enzyme catalysis are comprehensively reviewed with
a particular focus on metabolic engineering, i.e. the rational improvement of
a cells metabolic functions using recombinant DNA technology. Genome sequencing and post-genomics approaches to strain improvement for amino
acid production will be covered as their impact, although already quite visible,
is expected to increase considerably in the future accelerating the development
of new and more efcient biocatalysts for amino acid production.
We are grateful to the authors who contributed excellent chapters to the
volume Amino Acids Pathways, Regulation and Metabolic Engineering. We
highly appreciate the expertise and enthusiasm devoted to their chapters.
Despite their many other obligations and duties their comprehensive overview
chapters were timely completed. Our thanks also go to Springer for publishing
this monograph and especially to Christina Eckey and Jutta Lindenborn for
their valuable suggestions and support.
Mnster, January 2007

Volker F. Wendisch
Alexander Steinbchel

Preface

VII

References
Aida K, Chibata I, Nakayama K, Takinami K, Yamada H (1986) Biotechnology of Amino
Acid Production. Progress in Industrial Microbiology. Kodansha Ltd, Tokyo and Elsevier,
AmsterdamOxfordNew YorkTokyo
Chambers I, Frampton J, Goldfarb P, Affara N, McBain W, Harrison PR (1986) The structure
of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded
by the termination codon, TGA. EMBO J 5:12211227
Eggeling L, Bott M (2005) Handbook of Corynebacterium glutamicum. CRC Press (Taylor
Francis Group), Boca Raton
Enei H, Yokozeki K, Akashi K (1989) Recent progress in microbial production of amino
acids. Gordon and Breach, Amsterdam
Hao B, Gong W, Ferguson TK, James CM, Krzycki JA, Chan MK (2002) A new UAG-encoded
residue in the structure of a methanogen methyltransferase. Science 296:14621466
Lobanov AV, Kryikov GV, Hateld DF, Gladyshev VN (2006) Is there a twenty third amino
acid in the genetic code? Trends Genet 22:357360
Srinivasan G, James CM, Krzycki JA (2002) Pyrrolysine encoded by UAG in Archaea: charging of a UAG-decoding specialized tRNA. Science 296:14591462
Sudarsan N, Wickiser JK, Nakamura S, Ebert MS, Breaker RR (2003) An mRNA structure in
bacteria that controls gene expression by binding lysine. Genes Dev 17:26882697
Yamada K, Kinoshita S, Tsunoda T, Aida K (1972) The microbial production of amino acid.
Kodansha Ltd, Tokyo
Zinoni F, Birkmann A, Stadtman TC, Bock A (1986) Nucleotide sequence and expression of the selenocysteine-containing polypeptide of formate dehydrogenase (formatehydrogen-lyase-linked) from Escherichia coli. Proc Natl Acad Sci USA 83:46504654

Contents

Production of Glutamate and Glutamate-Related Amino Acids:

Molecular Mechanism Analysis and Metabolic Engineering
H. Shimizu T. Hirasawa . . . . . . . . . . . . . . . . . . . . . . . . . .

The l-Lysine Story:

From Metabolic Pathways to Industrial Production
C. Wittmann J. Becker . . . . . . . . . . . . . . . . . . . . . . . . . . .

39

L-Threonine
M. Rieping T. Hermann . . . . . . . . . . . . . . . . . . . . . . . . . .

71

Aromatic Amino Acids

G. A. Sprenger . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

93

Branched-Chain Amino Acids

M. Ptek . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Methionine Biosynthesis
in Escherichia coli and Corynebacterium glutamicum
R. M. Figge . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Cysteine Metabolism and Its Regulation in Bacteria
E. Gudon I. Martin-Verstraete . . . . . . . . . . . . . . . . . . . . . . 195
Microbial Arginine Biosynthesis:
Pathway, Regulation and Industrial Production
N. Glansdorff Y. Xu . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
l-Serine and Glycine
L. Eggeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Alanine, Aspartate, and Asparagine Metabolism in Microorganisms
T. Oikawa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273

Contents

Amino Acid Transport Systems

in Biotechnologically Relevant Bacteria
K. Marin R. Krmer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
Occurrence, Biosynthesis,
and Biotechnological Production of Dipeptides
S. Hashimoto . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
Genomes and Genome-Level Engineering
of Amino Acid-Producing Bacteria
H. Yukawa M. Inui A. A. Verts . . . . . . . . . . . . . . . . . . . . . 349
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403