Physiological effects, biosynthesis, and derivatization of key human milk tetrasaccharides, lacto-<i>N</i>-tetraose, and lacto-<i>N</i>-neotetraose

Zhu, Yingying; Luo, Guocong; Wan, Li; Meng, Jiawei; Lee, Sang Yup; Mu, Wanmeng

doi:10.1080/07388551.2021.1944973

Cited by 24 publications

(45 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For LNT II biosynthesis, a bacterial β-1,3- N -acetylglucosaminyltransferase (LgtA, EC 2.4.1.149), which catalyzes LNT II synthesis from the exogenously added lactose and the endogenously synthesized UDP- N -acetylglucosamine (UDP-GlcNAc), should be introduced into the engineered host strains. Then, WbgO is further introduced to catalyze the transgalactosylation of LNT II from the endogenously synthesized UDP-Gal to produce LNT …”

Section: Resultsmentioning

confidence: 99%

“…More than 200 structurally different HMOs have been identified in human milk to date, and they constitute the major difference between human milk and animal milk . Clinical studies indicate that the HMO-added formula is safe and shows a similar growth pattern as breast-fed infants. , To date, at least seven different HMOs have received the Generally Recognized as Safe (GRAS) status for use as functional fortifiers from the Food and Drug Administration (FDA) of US, and six of them have been commercially added in various brands of the infant formula …”

Section: Introductionmentioning

confidence: 99%

“…Lacto- N -tetraose (LNT) is composed of galactose, N -acetylglucosamine, and glucose moieties, structurally shown as Galβ1,3GlcNAcβ1,3Galβ1,4Glc. It is not only a basic component in HMOs, accounting for approximately 6% (w/w) of the total HMOs, but also an important core structure which can be further fucosylated or sialylated to other HMOs . The physiological effects of LNT have been widely determined, including the prebiotic effect, preventing necrotizing enterocolitis, antiadhesive/antimicrobial activity, and antiviral protection .…”

Section: Introductionmentioning

confidence: 99%

“…By comparison, β-1,3-GalT has a better practical significance for LNT biosynthesis because its substrate, UDP-Gal, is an intermediate in cell metabolism and is easy to be accumulated through the metabolic engineering approach . Based on strengthening UDP-Gal accumulation and construction of the LNT II biosynthesis pathway, introduction of an LNT-forming β-1,3-GalT can efficiently produce LNT by the cell factory approach.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Metabolic Engineering of Escherichia coli for Efficient Biosynthesis of Lacto-N-tetraose Using a Novel β-1,3-Galactosyltransferase from Pseudogulbenkiania ferrooxidans

Zhu

Luo

et al. 2021

J. Agric. Food Chem.

Self Cite

View full text Add to dashboard Cite

Human milk oligosaccharides (HMOs) attract considerable interest in recent years because of their particular role in infant health. Lacto-N-tetraose (LNT), one of the most abundant HMOs, has been commercially added in the infant formula as a functional fortifier. In this study, a novel LNT-producing β-1,3-galactosyltransferase (β-1,3-GalT) from Pseudogulbenkiania ferrooxidans was screened from 14 putative candidates, and a highly LNT-producing metabolically engineered Escherichia coli strain was constructed based on a previously constructed lacto-N-triose II (LNT II)-producing strain, by strengthening UDP-galactose synthesis and introduction of P. ferrooxidans β-1,3-GalT. The engineered strain produced 3.11 and 25.49 g/L LNT in shake-flask and fed-batch cultivation, with the molar conversion ratio of LNT II to LNT of 88.15 and 85.09%, respectively. The productivity and specific yield of LNT in fed-batch cultivation were measured to be 0.61 g/L·h and 0.76 g/g dry cell weight, respectively. To the best of our knowledge, it is the highest LNT yield ever reported.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metabolic Engineering of Escherichia coli for Efficient Biosynthesis of Lacto-N-tetraose Using a Novel β-1,3-Galactosyltransferase from Pseudogulbenkiania ferrooxidans

Zhu

Luo

et al. 2021

J. Agric. Food Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Human milk oligosaccharides (HMOs) are recently attracting increasing attention, as they have numerous excellent physiological functions in human infants, such as promoting brain development in the newborn [ 1 , 2 ], improving their intelligence [ 3 ], avoiding infection [ 4 , 5 ], and acting as prebiotics [ 6 ]. To date, more than 200 different structures have been found and identified in HMOs, composed of five various monosaccharides including glucose (Glc), galactose (Gal), N -acetylglucosamine (GlcNAc), L-fucose (Fuc), and sialic acid (SA) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Engineering Escherichia coli for highly efficient production of lacto-N-triose II from N-acetylglucosamine, the monomer of chitin

Zhu

et al. 2021

Biotechnol Biofuels

Self Cite

View full text Add to dashboard Cite

Background Lacto-N-triose II (LNT II), an important backbone for the synthesis of different human milk oligosaccharides, such as lacto-N-neotetraose and lacto-N-tetraose, has recently received significant attention. The production of LNT II from renewable carbon sources has attracted worldwide attention from the perspective of sustainable development and green environmental protection. Results In this study, we first constructed an engineered E. coli cell factory for producing LNT II from N-acetylglucosamine (GlcNAc) feedstock, a monomer of chitin, by introducing heterologous β-1,3-acetylglucosaminyltransferase, resulting in a LNT II titer of 0.12 g L−1. Then, lacZ (lactose hydrolysis) and nanE (GlcNAc-6-P epimerization to ManNAc-6-P) were inactivated to further strengthen the synthesis of LNT II, and the titer of LNT II was increased to 0.41 g L−1. To increase the supply of UDP-GlcNAc, a precursor of LNT II, related pathway enzymes including GlcNAc-6-P deacetylase, glucosamine synthase, and UDP-N-acetylglucosamine pyrophosphorylase, were overexpressed in combination, optimized, and modulated. Finally, a maximum titer of 15.8 g L−1 of LNT II was obtained in a 3-L bioreactor with optimal enzyme expression levels and β-lactose and GlcNAc feeding strategy. Conclusions Metabolic engineering of E. coli is an effective strategy for LNT II production from GlcNAc feedstock. The titer of LNT II could be significantly increased by modulating the gene expression strength and blocking the bypass pathway, providing a new utilization for GlcNAc to produce high value-added products.

show abstract

Differences in the content of human milk oligosaccharides between foremilk and hind milk

Sun

Liu

et al. 2023

Food Bioengineering

View full text Add to dashboard Cite

Human milk oligosaccharides (HMOs) are the second largest carbohydrate component and the third largest nutrient after lactose, and their content and composition are related to the genetic characteristics of the mother, lactation period, geography, and other factors. This study examined the differences in fat content, protein composition, and oligosaccharides content between foremilk and hind milk in human milk. The results showed that the fat content of human milk was significantly higher in the hind milk than in the foremilk. However, no significant differences in the composition and content of protein in the fore and hind milk. With respect to oligosaccharides, the total amount of HMOs (based on seven oligosaccharides, lacto-N-neotetraose (LNnT), lacto-N-tetraose (LNT), 2′-fucosyllactose (2′-FL), 3′-fucosyllactose (3′-FL), 3′-galactosyllactose (3′-GL), 3′-sialyllactose (3′-SL), and 6′-sialyllactose (6′-SL) in the hind milk was always higher than in the foremilk in almost all mothers. Similar trend was found in specific oligosaccharide including LNnT, LNT, 2′-FL, 3′-FL, and 3′-GL. On the other hand, sialylated oligosaccharides, 3′-SL, and 6′-SL were quite consistent in foremilk and hind milk.

show abstract

Physiological effects, biosynthesis, and derivatization of key human milk tetrasaccharides, lacto-N-tetraose, and lacto-N-neotetraose

Cited by 24 publications

References 112 publications

Metabolic Engineering of Escherichia coli for Efficient Biosynthesis of Lacto-N-tetraose Using a Novel β-1,3-Galactosyltransferase from Pseudogulbenkiania ferrooxidans

Metabolic Engineering of Escherichia coli for Efficient Biosynthesis of Lacto-N-tetraose Using a Novel β-1,3-Galactosyltransferase from Pseudogulbenkiania ferrooxidans

Engineering Escherichia coli for highly efficient production of lacto-N-triose II from N-acetylglucosamine, the monomer of chitin

Differences in the content of human milk oligosaccharides between foremilk and hind milk

Contact Info

Product

Resources

About