Genetically engineered microorganisms for the production of poly-4-hydroxybutyrate
A technology of hydroxybutyrate and products, applied in the field of genetically engineered microorganisms for the production of poly-4-hydroxybutyrate, which can solve the problems of low cytotoxicity, low amount of desired product, low polymer, etc.
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Embodiment 1
[0199] Example 1: Improvement of P4HB production by using alpha-ketoglutarate decarboxylase from Pseudonocardia dioxanivorans
[0200] Several metabolic pathways have been proposed to produce succinic semialdehyde (SSA) from the tricarboxylic acid (TCA) cycle (reviewed by Steinbüchel and Lütke-Eversloh, Biochem. Engineering J. 16:81–96 (2003) and Efe et al., Biotechnology and Bioengineering 99:1392-1406 (2008)). One such pathway converts α-ketoglutarate to SSA by α-ketoglutarate decarboxylase encoded by kgdM (Tian et al., Proc. Natl. Acad. Sci. U.S.A. 102:10670-10675 (2005)). Previous attempts have utilized the kgdM gene from Mycobacterium tuberculosis (Tian et al., Proc. Natl. Acad. Sci. U.S.A. 102:10670-10675 (2005); figure 1 , Reaction No. 6) The production of P4HB was not successful, and only a very small amount of P4HB was produced (Van Walsem et al., patent application number WO 2011100601A1).
[0201] This example demonstrates that homologues of M. tuberculosis KgdM ...
Embodiment 2
[0210] Example 2: Development of a growth selection strategy to obtain genes with improved α-ketoglutarate decarboxylase activity
[0211] The P4HB titers of recombinant hosts expressing the kgd homologue from P.dioxanivorans (hereafter referred to as kgdP) were only positive for those expressing sucD from Clostridium krujiri. Ck Approximately two-thirds of the titers were obtained in strains with the * gene (see Tables 2 and 3). Therefore, a growth selection method was developed to obtain mutated kgdP genes with improved α-ketoglutarate decarboxylase activity. To this end, Escherichia coli MG1655ΔsucAB strain was constructed, which lacked α-ketoglutarate dehydrogenase activity ( figure 1 , Reaction 4). MG1655 containing the deletion of sucAB was constructed using the above-mentioned known biotechnology means and methods. Due to the lack of α-ketoglutarate dehydrogenase (ΔsucAB) and any native α-ketoglutarate decarboxylase activity in E. Grow in E2 minimal medium as the s...
Embodiment 3
[0215] Example 3: Improved P4HB production by expressing a mutated alpha-ketoglutarate decarboxylase kgdP-M38 from Pseudonocardia dioxanivorans
[0216] Improved P4HB production in strains expressing kgdP-M38
[0217] In this example, the production of P4HB was compared in strains expressing native kgdP and in strains expressing the mutated kgdP-M38 from Pseudonocardia dioxanivorans. Therefore, the following two strains were constructed using the well-known biotechnological tools and methods described above, the genomes of both strains contain chromosomal deletions of yneI, gabD, pykF and pykA, and overexpression of orfZ from Clostridium krusii Ck genes, ppc gene from Escherichia coli, PHA synthase phaC3 / C1* and ssaR from Arabidopsis At *Gene. In addition, strain 7 with P trc The promoter expresses the native kgdP gene, while strain 8 also expresses the P trc The promoter expressed mutated kgdP-M38 (Table 5).
[0218] Table 5: Microbial strains used in this part of Exampl...
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