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l-Methionine Production

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Amino Acid Fermentation

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 159))

Abstract

l-Methionine has been used in various industrial applications such as the production of feed and food additives and has been used as a raw material for medical supplies and drugs. It functions not only as an essential amino acid but also as a physiological effector, for example, by inhibiting fat accumulation and enhancing immune response. Producing methionine from fermentation is beneficial in that microorganisms can produce l-methionine selectively using eco-sustainable processes. Nevertheless, the fermentative method has not been used on an industrial scale because it is not competitive economically compared with chemical synthesis methods. Presented are efforts to develop suitable strains, engineered enzymes, and alternative process of producing l-methionine that overcomes problems of conventional fermentation methods. One of the alternative processes is a two-step process in which the l-methionine precursor is produced by fermentation and then converted to l-methionine by enzymes. Directed efforts toward strain development and enhanced enzyme engineering will advance industrial production of l-methionine based on fermentation.

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Notes

  1. 1.

    Throughout text, sequence alignment was performed using Clustal-O and structure superposition with the FATCAT-server (rigid pairwise alignment). The VMD program was used to visualize the alignments. IDs (Uniprot) of sequences used in this review are as follows: MetA (B. cereus): Q72X44, MetA (T. maritima): Q9WZY3, MetA (E. coli): P07623, MetX (P. aeruginosa): P57714, MetX (P. putida): Q88CT3, MetX (P. syringae): Q4ZZ78, MetX (H. influenzae): P45131, MetX (S. cerevisiae): P08465, MetX (L. interrogans): Q8F4I0.

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  1. Research Institute of Biotechnology, CJ CheilJedang Corp., CJ Blossom Park. 55, Gwanggyo-ro 42beon-gil, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16495, South Korea

    Jihyun Shim, Yonguk Shin, Imsang Lee & So Young Kim

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  2. Yonguk Shin
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  1. Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan

    Atsushi Yokota

  2. Faculty of Agriculture, Shinshu University, Nagano, Japan

    Masato Ikeda

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Fig. S1Fig. S2Fig. S3Fig. S4Fig. S5

Key residues in the active site of MetA of B. cereus. Residues shown in stick models are Ala108 and Trp143 consisting oxyanion hole. Lys163, Glu246 and Arg249 play a role holding amino- and carboxylic acid groups of homoserine shown in spherical representations colored transparent. Lys46 is shown away from the catalytic site (PDF 1697 kb)

Residues showing reduced feedback regulations upon mutations in MetA of E. coli. Structure of MetA of E. coli is built by homology modeling using Modeller (v9.2). Considering similar responses to heat, MetA of E. coli was modeled using MetA of B. cereus instead of MetA of T. maritima. Except for mutations on N-terminal 1-33 residues and C-terminal 297- residues, following residues are shown; Represented as ball-and-stick model is residues 58-65, 292-298, Asp101, Asn290 and Tyr291. Shown in stick model is Asn79, Glu114, Phe140, Lys163, Phe222 and Ala275. Overall structure of MetA is in the same orientation with Fig. 2 (PDF 1697 kb)

Mutation sites increasing thermostability of MetA of E. coli; Ser61, Glu213, Ile229, Asn267, and Asn271 (stick-representation). Overall structure of MetA is in the same orientation with Figs. S2 and 2 (PDF 1697 kb)

Sequence alignment of MetXs from different species, P. aeruginosa, L. interrogans, H. influenzae, S. cerevisiae, P. putida, and P. syringae. A. Largest differences arise in N- and C-terminus and additionally MetX of S. cerevisiae has much larger capping domain shown in green box. Residues in yellow box compose a unique loop in MetX which corresponds to the location of Glu/Gly111 of MetA. B. Sequence of MetX of P. aeruginosa has high similarity with its close species, P. putida and P. syringae (PDF 1697 kb)

Sequence alignment of the γ-elimination subclass of the Cys/Met metabolism PLP-dependent family of enzymes, MetB, MetY and MetZ from various bacteria. MetB_Eco (E .coli MetB, PDB entry 1CS1), MetZ_Mtu (M. tuberculosis MetZ, PDB entry 3NDN), MetB_Cgl (C. glutamicum MetB), MetY_Cgl (C. glutamicum MetY), MetY_Pae (P. aeruginosa MetY), MetZ_Pae (P. aeruginosa MetZ), MetY_Lme (L. meyeri MetY), MetZ_Ppu (P. putida MetZ), MetZ_Cvi (C. violaceum MetZ), MetZ_Hne (H. neptunium MetZ), MetZ_Nfa (N. farcinica MetZ), MetZ_Rsp (R. sphaeroides MetZ). Numbering is for E. coli MetB. Conserved residues are shown in boxes with white font and red shading. Conservative substitutions are shown in boxes with a red font. The conserved active site lysine is marked with asterisk. The two conserved residues from the N-terminal domain of an adjacent monomer, which are predicted to bind to the PLP phosphate group, are marked with red triangles. Insertions that are a characteristic of OAHS members are indicated by orange box. Sequence alignment was done using Clustal Omega and Espript 3.0 (PDF 1697 kb)

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Shim, J., Shin, Y., Lee, I., Kim, S.Y. (2016). l-Methionine Production. In: Yokota, A., Ikeda, M. (eds) Amino Acid Fermentation. Advances in Biochemical Engineering/Biotechnology, vol 159. Springer, Tokyo. https://doi.org/10.1007/10_2016_30

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