Increase in the Rate ofL-Pipecolic Acid Production Usinglat-ExpressingEscherichia colibylysPandyeiEAmplification

Identification of ArgP and Lrp as Transcriptional Regulators of lysP, the Gene Encoding the Specific Lysine Permease of Escherichia coli

“…2). Based on this motif and previous data from the literature (2,8,16,50), three LTTRs were selected as putative transcriptional regulators of lysP: LysR, YeiE, and ArgP. LysR is the activator protein required for expression of lysA, which encodes the enzyme that catalyzes the last step in lysine biosynthesis, the decarboxylation of diaminopimelate (DAP), into lysine (50).…”

Investigation of the biosynthesis of the pipecolate moiety of neuroprotective polyketide meridamycin

“…However, E. coli P5C reductase, which catalyzes the terminal step in proline biosynthesis, was found to be able to efficiently catalyze the conversion of P6C into pipecolate. 23 It was possible that in microorganisms that utilize the P6C pathway to produce pipecolate, this universally conserved P5C reductase might be responsible for the reduction of P6C to L-pipecolic acid. Therefore, inactivation of this gene might be sufficient to block the majority of pipecolate production in Streptomyces sp.…”

Enzymatic Synthesis ofL-Pipecolic Acid by Δ1-Piperideine-2-carboxylate Reductase fromPseudomonas putida

“…An enzymatic system for the synthesis of L-pipecolic acid from L-lysine by commercial L-lysine -oxidase from Trichoderma viride and an extract of recombinant Escherichia coli cells coexpressing Á 1 -piperideine-2-carboxylate reductase from Pseudomonas putida and glucose dehydrogenase from Bacillus subtilis is described. A laboratory-scale process provided 27 g/l of Lpipecolic acid in 99.7% e.e.Key words: Á 1 -piperideine-2-carboxylate reductase; Pseudomonas putida; L-pipecolic acid; Á 1 -piperideine-2-carboxylate L-Pipecolic acid, a nonproteinogenic -amino acid, is a key component of many bioactive molecules, such as the immunosuppressant FK506, 1) the anticancer agent VX710, 2) the antifungal antibiotic demethoxyrapamycin,3) the N-methyl-D-aspartate antagonist selfotel, 4) the antitumor antibiotic sandramycin, 5) the phytotoxic metabolite Cyl-2, 6) the anesthetic bupivacaine, 7) and the HIV protease inhibitor palinavir.8) There is an increasing demand for a convenient and efficient synthetic route to enantiomerically pure L-pipecolic acid because of its use in the synthesis of new medicaments.Current methods to obtain a pure enantiomer of L-pipecolic acid involve chemical resolution, 9) stereoselective transformation, 10) the derivatization of natural amino acids, 11) and enzymatic reactions, [12][13][14][15][16] but most of these methods fail to provide a satisfactory solution for the synthesis of chiral pipecolic acid on an industrial scale due to certain limitations, such as tedious procedures, low yields, and unavailability of starting materials. Hence, new and convenient methods for the preparation of optically active pipecolic acid are required.…”

“…Current methods to obtain a pure enantiomer of L-pipecolic acid involve chemical resolution, 9) stereoselective transformation, 10) the derivatization of natural amino acids, 11) and enzymatic reactions, [12][13][14][15][16] but most of these methods fail to provide a satisfactory solution for the synthesis of chiral pipecolic acid on an industrial scale due to certain limitations, such as tedious procedures, low yields, and unavailability of starting materials. Hence, new and convenient methods for the preparation of optically active pipecolic acid are required.…”

“…22) Fujii et al reported the synthesis of L-pipecolic acid from L-lysine using recombinant E. coli cells expressing L-lysine 6-aminotransferase and pyrroline-5-carboxylate reductase. 12,13) In their system, at most 16 g/l of Lpipecolic acid is synthesized in a 110-h reaction.…”