Microbial Metabolic Engineering for L-Threonine Production

L-threonine, one of the three major amino acids produced throughout the world, has a wide application in industry, as an additive or as a precursor for the biosynthesis of other chemicals. It is predominantly produced through microbial fermentation the ef

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Microbial Metabolic Engineering for L-Threonine Production Xunyan Dong, Peter J. Quinn, and Xiaoyuan Wang

Abstract L-threonine, one of the three major amino acids produced throughout the world, has a wide application in industry, as an additive or as a precursor for the biosynthesis of other chemicals. It is predominantly produced through microbial fermentation the efficiency of which largely depends on the quality of strains. Metabolic engineering based on a cogent understanding of the metabolic pathways of L-threonine biosynthesis and regulation provides an effective alternative to the traditional breeding for strain development. Continuing efforts have been made in revealing the mechanisms and regulation of L-threonine producing strains, as well as in metabolic engineering of suitable organisms whereby genetically-defined, industrially competitive L-threonine producing strains have been successfully constructed. This review focuses on the global metabolic and regulatory networks responsible for L-threonine biosynthesis, the molecular mechanisms of regulation, and the strategies employed in strain engineering. Keywords L-threonine biosynthesis • L-threonine production • Metabolic engineering • Regulation mechanism

X. Dong Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, JiangnanUniversity, Wuxi 214122, China P.J. Quinn Department of Biochemistry, King’s College London, 150 Stamford Street, London SE1 9NH, United Kingdom Wang () State Key Laboratory of Food Science and Technology, School of Biotechnology, JiangnanUniversity, Wuxi 214122, China e-mail: [email protected] X. Wang et al. (eds.), Reprogramming Microbial Metabolic Pathways, Subcellular Biochemistry 64, DOI 10.1007/978-94-007-5055-5_14, © Springer Science+Business Media Dordrecht 2012

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Abbreviations SD sequence ACT

14.1

Shine-Dalgarno sequence Aspartate kinase, Chorismate mutase and TyrA

Introduction

L-threonine is currently one of the three major amino acids produced throughout the world with an annual market size of approximate 0.23 metric tons (Becker and Wittmann 2011). Among its wide industrial application, the most remarkable use of L-threonine is as a feed additive. Application of low protein level formula feeds supplemented with L-threonine improves the growth of livestock, relieves crude protein deficiency and lowers nitrogen emissions, thus contributing to the sustainable development of the society. Recent studies acknowledging L-threonine as the second and the third limiting amino acid in swine and poultry feeds respectively (Ajinomoto 2009) have stimulated the further expansion of the industry. Moreover, L-threonine can be used as precursor for the biosynthesis of L-isoleucine and L-homoalanine. This underpins recent developments in the efficient microbial production of L-threonine (Leuchtenberger et al. 2005). The most efficient solution to improve productivity of the bioconversion and reduce costs is to develop highly productive strains. Thanks to traditio