Engineering an aldehyde dehydrogenase toward its substrates, 3-hydroxypropanal and NAD+, for enhancing the production of 3-hydroxypropionic acid

Park, Ye Seop; Choi, Un Jong; Nam, Nguyễn Hoài; Choi, Sang Jin; Nasır, Abdul; Lee, Sun‐Gu; Kim, Kyung Jin; Jung, Gyoo Yeol; Choi, Sangdun; Shim, Jeung Yeop; Park, Sunghoon; Yoo, Tae Hyeon

doi:10.1038/s41598-017-15400-x

Cited by 23 publications

(10 citation statements)

References 74 publications

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“…The production of a proposed intermediate (I-4) for this fermentation was also previously implicated as a product of fermentation [ 40 ]. 3-Hydroxypropanal (I-5), otherwise known as lactaldehyde, is naturally produced from glycerol and is predominant in all living organisms including humans and bacteria [ 41 ]. The molecule (I-5) links with lactic acid production during fermentation [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Fermentation Enhanced Biotransformation of Compounds in the Kernel of Chrysophyllum albidum

et al. 2020

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Chrysophyllum albidum Linn (African star apple) is a fruit with extensive nutritional and medicinal benefits. The fruit and kernel in the seed are both edible. Strains of lactic acid bacteria (LAB) were isolated from fermented seeds and assessed for probiotic characteristics. The extracts in both the unfermented and the fermented aqueous extracts from the kernels obtained from the seeds of C. albidum were subjected to analysis using the gas chromatography/mass spectrometry (GC-MS) method. This analysis identified the bioactive compounds present as possible substrate(s) for the associated organisms inducing the fermentation and the resultant biotransformed products formed. Three potential probiotic LAB strains identified as Lactococcus raffinolactis (ProbtA1), Lactococcus lactis (ProbtA2a), and Pediococcus pentosaceus (ProbtA2b) were isolated from the fermented C. albidum seeds. All strains were non hemolytic, which indicated their safety, Probt (A1, A2a, and A2b) grew in an acidic environment (pH 3.5) during the 48-h incubation time, and all three strains grew in 1% bile, and exhibited good hydrophobicity and auto-aggregation properties. Mucin binding proteins was not detected in any strain, and bile salt hydrolase was detected in all the strains. l-lactic acid (28.57%), norharman (5.07%), formyl 7E-hexadecenoate (1.73%), and indole (1.51%) were the four major constituents of the fermented kernel of the C. albidum, while 2,5-dimethylpyrazine (C1, 1.27%), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (C2, 2.90%), indole (C3, 1.31%), norharman (C4, 3.01%), and methyl petroselinate (C5, 4.33%) were the five major constituents of the unfermented kernels. The isolated LAB are safe for consumption. The fermenting process metabolized C1, C2, and C5, which are possible starter cultures for the growth of probiotics. Fermentation is an essential tool for bioengineering molecules in foods into safe and health beneficial products.

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Section: Discussionmentioning

confidence: 99%

Fermentation Enhanced Biotransformation of Compounds in the Kernel of Chrysophyllum albidum

et al. 2020

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“…The structure of KGSADH has been solved and has provided a basis for rational enzyme engineering. This has yielded enzyme variants with improved activity toward 3-HPA (Park et al, 2017; Son et al, 2017; Seok et al, 2018).…”

Section: The Suite Of Enzymes Used In Heterologous 3-hp Synthesis Patmentioning

confidence: 99%

Production of 3-Hydroxypropanoic Acid From Glycerol by Metabolically Engineered Bacteria

Jers

Kalantari

Garg

et al. 2019

Front. Bioeng. Biotechnol.

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3-hydroxypropanoic acid (3-HP) is a valuable platform chemical with a high demand in the global market. 3-HP can be produced from various renewable resources. It is used as a precursor in industrial production of a number of chemicals, such as acrylic acid and its many derivatives. In its polymerized form, 3-HP can be used in bioplastic production. Several microbes naturally possess the biosynthetic pathways for production of 3-HP, and a number of these pathways have been introduced in some widely used cell factories, such as Escherichia coli and Saccharomyces cerevisiae . Latest advances in the field of metabolic engineering and synthetic biology have led to more efficient methods for bio-production of 3-HP. These include new approaches for introducing heterologous pathways, precise control of gene expression, rational enzyme engineering, redirecting the carbon flux based on in silico predictions using genome scale metabolic models, as well as optimizing fermentation conditions. Despite the fact that the production of 3-HP has been extensively explored in established industrially relevant cell factories, the current production processes have not yet reached the levels required for industrial exploitation. In this review, we explore the state of the art in 3-HP bio-production, comparing the yields and titers achieved in different microbial cell factories and we discuss possible methodologies that could make the final step toward industrially relevant cell factories.

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“…The enzymes also displayed higher substrate specificities for aldehyde and NAD + and weaker inhibition by NADH. Furthermore, the recombinant Pseudomonas denitrificans strain carrying one of KGSADH variants exhibited less 3‐HPA and higher cell growth compared with the wild‐type KGSADH . The second approach for improving 3‐HP production may be promoter engineering, by which sufficient RNA polymerases (RNAPs) can be recruited and thus facilitate PuuC expression and boost 3‐HP production .…”

Section: Discussionmentioning

confidence: 99%

Physiological investigations of the influences of byproduct pathways on 3‐hydroxypropionic acid production in Klebsiella pneumoniae

Chen

Wang

et al. 2019

J Basic Microbiol

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Klebsiella pneumoniae can naturally synthesize 3‐hydroxypropionic acid (3‐HP), 1,3‐propanediol (1,3‐PD), and 2,3‐butanediol (2,3‐BD) from glycerol. However, biosynthesis of these industrially important chemicals is constrained by troublesome byproducts. To clarify the influences of byproducts on 3‐HP production, in this study, a total of eight byproduct‐producing enzyme genes including pmd, poxB, frdB, fumC, dhaT, ilvH, adhP, and pflB were individually deleted from the K. pneumoniae genome. The resultant eight mutants presented different levels of metabolites. In 24‐h shake‐flask cultivation, the adhP‐ and pflB‐deletion mutants produced 0.41 and 0.44 g/L 3‐HP, respectively. Notably, the adhP and pflB double deletion mutant K. pneumoniaeΔadhPΔpflB produced 1.58 g/L 3‐HP in 24‐h shake‐flask cultivation. When K. pneumoniaeΔadhPΔpflB was harnessed as a host strain to overexpress PuuC, a native aldehyde dehydrogenase (ALDH) catalyzing 3‐hydroxypropionaldehyde (3‐HPA) to 3‐HP, the resulting recombinant strain K. pneumoniaeΔadhPΔpflB(pTAC‐puuC) (pTAC‐puuC is PuuC expression vector) generated 66.91 g/L 3‐HP with a cumulative yield of 70.84% on glycerol in 60‐h bioreactor cultivation. Additionally, this strain showed 2.3‐, 5.1‐, and 0.67‐fold decrease in the concentrations of 1,3‐PD, 2,3‐BD, and acetic acid compared with the reference strain K. pneumoniae(pTAC‐puuC). These results indicated that the byproducts exerted differential impacts on the production of 3‐HP, 1,3‐PD, and 2,3‐BD. Although combinatorial elimination of byproduct pathways could reprogram glycerol flux, the enzyme 1,3‐propanediol oxidoreductase (DhaT) that catalyzes 3‐HPA to 1,3‐PD and the enzymes ALDHs, especially, PuuC are most pivotal for 3‐HP production. This study provides a deep understanding of how byproducts affect the production of 3‐HP, 1,3‐PD, and 2,3‐BD in K. pneumoniae.

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Engineering an aldehyde dehydrogenase toward its substrates, 3-hydroxypropanal and NAD+, for enhancing the production of 3-hydroxypropionic acid

Cited by 23 publications

References 74 publications

Fermentation Enhanced Biotransformation of Compounds in the Kernel of Chrysophyllum albidum

Fermentation Enhanced Biotransformation of Compounds in the Kernel of Chrysophyllum albidum

Production of 3-Hydroxypropanoic Acid From Glycerol by Metabolically Engineered Bacteria

Physiological investigations of the influences of byproduct pathways on 3‐hydroxypropionic acid production in Klebsiella pneumoniae

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