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Microbial production of lactate-containing polyesters.

Yang JE, Choi SY, Shin JH, Park SJ, Lee SY - Microb Biotechnol (2013)

Bottom Line: Systems metabolic engineering integrating traditional metabolic engineering with systems biology, synthetic biology, protein/enzyme engineering through directed evolution and structural design, and evolutionary engineering, enabled microorganisms to efficiently produce natural and non-natural products.Here, we review the strategies for the metabolic engineering of microorganisms for the in vivo biosynthesis of lactate-containing polyesters and for the optimization of whole cell metabolism to efficiently produce lactate-containing polyesters.Also, major problems to be solved to further enhance the production of lactate-containing polyesters are discussed.

View Article: PubMed Central - PubMed

Affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Program), Center for Systems and Synthetic Biotechnology, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea; Institute for the BioCentury, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.

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Extended metabolic pathways for production of the 2-hydroxyacid containing PHAs. Lactate-containing copolymers can be produced by engineered Pct and PhaC using lactate and glycolate (C2), lactate (C3) or 2-hydroxybutyrate (C4) as substrates. Although lactate feeding is shown in this figure, it is also possible to produce it in vivo as shown in Fig. 5. Metabolic pathways for production of PHAs containing 2HB monomers using glucose as the sole carbon source (Park et al., 2012d). Cross represents the competitive pathway blocked. Abbreviations are: CimA, citramalate synthase; LeuBCD, 3-isopropylmalate dehydratase; PanE, D-2-hydroxyacid dehydrogenase. This figure is redrawn from a previous report (Park et al., 2012d).
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fig06: Extended metabolic pathways for production of the 2-hydroxyacid containing PHAs. Lactate-containing copolymers can be produced by engineered Pct and PhaC using lactate and glycolate (C2), lactate (C3) or 2-hydroxybutyrate (C4) as substrates. Although lactate feeding is shown in this figure, it is also possible to produce it in vivo as shown in Fig. 5. Metabolic pathways for production of PHAs containing 2HB monomers using glucose as the sole carbon source (Park et al., 2012d). Cross represents the competitive pathway blocked. Abbreviations are: CimA, citramalate synthase; LeuBCD, 3-isopropylmalate dehydratase; PanE, D-2-hydroxyacid dehydrogenase. This figure is redrawn from a previous report (Park et al., 2012d).

Mentions: The versatile substrate specificities of engineered class II PHA synthases allow further extending the monomer spectrum of in vivo PLA synthesis system for the incorporation of glycolate, lactate and 2-hydroxybutyrate monomers into polyesters (Fig. 6). Glycolate, the simplest and shortest member of 2-hydroxycarboxylates, could also be incorporated into PHAs by engineered Pseudomonas sp. 61-3 PHA synthase when glycolate was supplied into the culture medium as a precursor (Matsumoto et al., 2011). Activation of glycolate and lactate to glycolyl-CoA and lactyl-CoA were mediated by M. elsdenii Pct, where both glycolyl-CoA and lactyl-CoA were used for the copolymerization with MCL-3-hydroxyalkanoyl-CoAs supplied by P. aeruginosa enoyl-CoA hydratase. The resulting copolymers containing glycolate and MCL-3-hydroxyalkanoates had weight-average molecular weight of 34 000 (Matsumoto et al., 2011).


Microbial production of lactate-containing polyesters.

Yang JE, Choi SY, Shin JH, Park SJ, Lee SY - Microb Biotechnol (2013)

Extended metabolic pathways for production of the 2-hydroxyacid containing PHAs. Lactate-containing copolymers can be produced by engineered Pct and PhaC using lactate and glycolate (C2), lactate (C3) or 2-hydroxybutyrate (C4) as substrates. Although lactate feeding is shown in this figure, it is also possible to produce it in vivo as shown in Fig. 5. Metabolic pathways for production of PHAs containing 2HB monomers using glucose as the sole carbon source (Park et al., 2012d). Cross represents the competitive pathway blocked. Abbreviations are: CimA, citramalate synthase; LeuBCD, 3-isopropylmalate dehydratase; PanE, D-2-hydroxyacid dehydrogenase. This figure is redrawn from a previous report (Park et al., 2012d).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3815930&req=5

fig06: Extended metabolic pathways for production of the 2-hydroxyacid containing PHAs. Lactate-containing copolymers can be produced by engineered Pct and PhaC using lactate and glycolate (C2), lactate (C3) or 2-hydroxybutyrate (C4) as substrates. Although lactate feeding is shown in this figure, it is also possible to produce it in vivo as shown in Fig. 5. Metabolic pathways for production of PHAs containing 2HB monomers using glucose as the sole carbon source (Park et al., 2012d). Cross represents the competitive pathway blocked. Abbreviations are: CimA, citramalate synthase; LeuBCD, 3-isopropylmalate dehydratase; PanE, D-2-hydroxyacid dehydrogenase. This figure is redrawn from a previous report (Park et al., 2012d).
Mentions: The versatile substrate specificities of engineered class II PHA synthases allow further extending the monomer spectrum of in vivo PLA synthesis system for the incorporation of glycolate, lactate and 2-hydroxybutyrate monomers into polyesters (Fig. 6). Glycolate, the simplest and shortest member of 2-hydroxycarboxylates, could also be incorporated into PHAs by engineered Pseudomonas sp. 61-3 PHA synthase when glycolate was supplied into the culture medium as a precursor (Matsumoto et al., 2011). Activation of glycolate and lactate to glycolyl-CoA and lactyl-CoA were mediated by M. elsdenii Pct, where both glycolyl-CoA and lactyl-CoA were used for the copolymerization with MCL-3-hydroxyalkanoyl-CoAs supplied by P. aeruginosa enoyl-CoA hydratase. The resulting copolymers containing glycolate and MCL-3-hydroxyalkanoates had weight-average molecular weight of 34 000 (Matsumoto et al., 2011).

Bottom Line: Systems metabolic engineering integrating traditional metabolic engineering with systems biology, synthetic biology, protein/enzyme engineering through directed evolution and structural design, and evolutionary engineering, enabled microorganisms to efficiently produce natural and non-natural products.Here, we review the strategies for the metabolic engineering of microorganisms for the in vivo biosynthesis of lactate-containing polyesters and for the optimization of whole cell metabolism to efficiently produce lactate-containing polyesters.Also, major problems to be solved to further enhance the production of lactate-containing polyesters are discussed.

View Article: PubMed Central - PubMed

Affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Program), Center for Systems and Synthetic Biotechnology, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea; Institute for the BioCentury, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea.

Show MeSH
Related in: MedlinePlus