Exploiting tandem repetitive promoters for high-level production of 3-hydroxypropionic acid

Zhao, Peng; Ma, Chunlu; Xu, Libin; Tian, Pingfang

doi:10.1007/s00253-019-09772-5

Cited by 34 publications

(36 citation statements)

References 40 publications

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“…Another biosynthetic route based on glycerol metabolism has been extensively studied; the highest 3HP titer (102.6 g L −1 ) in the literature was obtained by engineered Klebsiella pneumoniae employing this route. [109] Also, this route facilitated the first homo poly(3HP) biosynthesis without supplementing any precursor. [63] Here, the three enzymes, glycerol dehydratase (DhaB1) from C. butyricum, propionaldehyde dehydrogenase (PduP) from S. enterica serovar Typhimurium LT2, and PhaC from C. necator were introduced in E. coli ( Figure 5).…”

Section: Poly(3hydroxypropionate)mentioning

confidence: 99%

Microbial Polyhydroxyalkanoates and Nonnatural Polyesters

et al. 2020

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Microorganisms produce diverse polymers for various purposes such as storing genetic information, energy, and reducing power, and serving as structural materials and scaffolds. Among these polymers, polyhydroxyalkanoates (PHAs) are microbial polyesters synthesized and accumulated intracellularly as a storage material of carbon, energy, and reducing power under unfavorable growth conditions in the presence of excess carbon source. PHAs have attracted considerable attention for their wide range of applications in industrial and medical fields. Since the first discovery of PHA accumulating bacteria about 100 years ago, remarkable advances have been made in the understanding of PHA biosynthesis and metabolic engineering of microorganisms toward developing efficient PHA producers. Recently, nonnatural polyesters have also been synthesized by metabolically engineered microorganisms, which opened a new avenue toward sustainable production of more diverse plastics. Herein, the current state of PHAs and nonnatural polyesters is reviewed, covering mechanisms of microbial polyester biosynthesis, metabolic pathways, and enzymes involved in biosynthesis of short‐chain‐length PHAs, medium‐chain‐length PHAs, and nonnatural polyesters, especially 2‐hydroxyacid‐containing polyesters, metabolic engineering strategies to produce novel polymers and enhance production capabilities and fermentation, and downstream processing strategies for cost‐effective production of these microbial polyesters. In addition, the applications of PHAs and prospects are discussed.

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Section: Poly(3hydroxypropionate)mentioning

confidence: 99%

Microbial Polyhydroxyalkanoates and Nonnatural Polyesters

et al. 2020

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“…It is worth mentioning that 3-HP has been listed as one of the top high value-added chemicals for development both in 2004 and 2010 by the U.S. Department of Energy ( Werpy et al, 2004 ; Bozell and Petersen, 2010 ). Bioconversion of 3-HP has already been extensively studied in many organisms, such as Escherichia coli , Klebsiella pneumoniae , and Saccharomyces cerevisiae ( Rathnasingh et al, 2010 ; Chen et al, 2014 ; Zhao et al, 2019 ), and a variety of substrates have been exploited to produce 3-HP ( Table 1 ). So far, the highest 3-HP titer was achieved in Halomonas bluephagenesis , which accumulated 154 g/L 3-HP in a 7-L bioreactor using 1,3-propanediol as substrate ( Jiang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Enhanced 3-Hydroxypropionic Acid Production From Acetate via the Malonyl-CoA Pathway in Corynebacterium glutamicum

Chang

Dai

Mao

et al. 2022

Front. Bioeng. Biotechnol.

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Acetate is an economical and environmental-friendly alternative carbon source. Herein, the potential of harnessing Corynebacterium glutamicum as a host to produce 3-hydroxypropionic acid (3-HP) from acetate was explored. First, the expression level of malonyl-CoA reductase from Chloroflexus aurantiacus was optimized through several strategies, strain Cgz2/sod-N-C* showed an MCR enzyme activity of 63 nmol/mg/min and a 3-HP titer of 0.66 g/L in flasks. Next, the expression of citrate synthase in Cgz2/sod-N-C* was weakened to reduce the acetyl-CoA consumption in the TCA cycle, and the resulting strain Cgz12/sod-N-C* produced 2.39 g/L 3-HP from 9.32 g/L acetate. However, the subsequent deregulation of the expression of acetyl-CoA carboxylase genes in Cgz12/sod-N-C* resulted in an increased accumulation of intracellular fatty acids, instead of 3-HP. Accordingly, cerulenin was used to inhibit fatty acid synthesis in Cgz14/sod-N-C*, and its 3-HP titer was further increased to 4.26 g/L, with a yield of 0.50 g 3-HP/g-acetate. Finally, the engineered strain accumulated 17.1 g/L 3-HP in a bioreactor without cerulenin addition, representing the highest titer achieved using acetate as substrate. The results demonstrated that Corynebacterium glutamicum is a promising host for 3-HP production from acetate.

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“…Third, optimization of 3-HP biosynthesis pathway was done by introducing an IPTG-inducible tac promoter in AldH ( puuC ) of K. pneumonia , which after further optimization in metabolic flux and fermentation conditions resulted in 83.8 g/L 3-HP . Further promoter engineering in the puuC , including tandem repetitive tac promoters, increased 3-HP titer to 102.61 g/L …”

Section: Introductionmentioning

confidence: 99%

Notable Improvement of 3-Hydroxypropionic Acid and 1,3-Propanediol Coproduction Using Modular Coculture Engineering and Pathway Rebalancing

Zhang

Zabed

Yun

et al. 2021

ACS Sustainable Chem. Eng.

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Sustainable bioconversion of glycerol into 3hydroxypropionic acid (3-HP) and 1,3-propanediol (1,3-PDO) is often bottlenecked by the accumulation of a toxic metabolic intermediate, 3-hydroxypropanaldehyde (3-HPA), mostly due to the imbalanced expression of the two key enzymes, namely, aldehyde dehydrogenase (AldH) and 1,3-PDO oxidoreductase (PDOR). Herein, we attempted to overcome it by modular coculture engineering using Lactobacillus reuteri and recombinant Escherichia coli strains through overexpressing an AldH (GabD4) and a PDOR (PduQ) in E. coli and pathway rebalancing via 5′untranslated region (5′-UTR) engineering in the gabD4 gene. We then used the L. reuteri−E. coli coculture systems in resting cell biocatalysis of glycerol under several technological configurations to produce 3-HP and 1,3-PDO. The conventional approach, which is a two-step process comprising resting cell production (first step) and biotransformation of glycerol with resting cells (second step), produced 51.36 g/L 3-HP and 34.27 g/L 1,3-PDO from 120 g/L glycerol, leaving more than 30 g/L glycerol unconverted. Subsequently, we did experiments in a modified approach, including one more biotransformation step with the two-step approach to convert the residual glycerol. This three-step approach increased glycerol consumption to 140 g/L and produced 71.62 g/L 3-HP and 47.68 g/L 1,3-PDO. Finally, the sequential feeding of glycerol and fresh cells notably improved glycerol consumption to 240 g/L and titers of 3-HP and 1,3-PDO to 125.93 and 88.46 g/L, respectively, with a net titer of 214.39 g/L, which was the highest titer ever reported. Therefore, modular coculture engineering with an appropriate technological configuration could have the potential for improved production of value-added chemicals, particularly 3-HP and 1,3-PDO.

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Exploiting tandem repetitive promoters for high-level production of 3-hydroxypropionic acid

Cited by 34 publications

References 40 publications

Microbial Polyhydroxyalkanoates and Nonnatural Polyesters

Microbial Polyhydroxyalkanoates and Nonnatural Polyesters

Enhanced 3-Hydroxypropionic Acid Production From Acetate via the Malonyl-CoA Pathway in Corynebacterium glutamicum

Notable Improvement of 3-Hydroxypropionic Acid and 1,3-Propanediol Coproduction Using Modular Coculture Engineering and Pathway Rebalancing

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