Production of HMOs using microbial hosts — from cell engineering to large scale production

Bych, Katrine; Mikš, Marta Hanna; Johanson, Ted; Hederos, Markus; Vigsnæs, Louise Kristine; Becker, Peter A.

doi:10.1016/j.copbio.2018.11.003

Cited by 164 publications

(172 citation statements)

References 41 publications

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“…These formula are supplemented with nondigestible carbohydrates (NDCs) such as galacto-oligosaccharides and inulin to mimic the health effects offered by HMOs. [7,8] A class of NDCs, commonly used in infant formulas are inulin-type fructans. Inulin-type fructans are generally isolated from chicory roots and composed of linear chains of (2-1)-linked fructose monomers with varying degree of polymerization (DP).…”

Section: Introductionmentioning

confidence: 99%

Fermentation of Chicory Fructo‐Oligosaccharides and Native Inulin by Infant Fecal Microbiota Attenuates Pro‐Inflammatory Responses in Immature Dendritic Cells in an Infant‐Age‐Dependent and Fructan‐Specific Way

Logtenberg

Akkerman

et al. 2020

Molecular Nutrition Food Res

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Scope Inulin‐type fructans are commonly applied in infant formula to support development of gut microbiota and immunity. These inulin‐type fructans are considered to be fermented by gut microbiota, but it is unknown how fermentation impacts immune modulating capacity and whether the process of fermentation is dependent on the infant's age. Methods and results The in vitro fermentation of chicory fructo‐oligosaccharides (FOS) and native inulin are investigated using pooled fecal inocula of two‐ and eight‐week‐old infants. Both inocula primarily utilize the trisaccharides in FOS, while they almost completely utilize native inulin with degree of polymerization (DP) 3–8. Fecal microbiota of eight‐week‐old infants degrades longer chains of native inulin up to DP 16. This correlates with a higher abundance of Bifidobacterium and higher production of acetate and lactate after 26 h of fermentation. Fermented FOS and native inulin attenuate pro‐inflammatory cytokines produced by immature dendritic cells (DCs), but profiles and magnitude of attenuation are stronger with native inulin than with FOS. Conclusion The findings demonstrate that fermentation of FOS and native inulin is dependent on the infant's age and fructan structure. Fermentation enhances attenuating effects of pro‐inflammatory responses in DCs, which depend mainly on microbial metabolites formed during fermentation.

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Section: Introductionmentioning

confidence: 99%

Fermentation of Chicory Fructo‐Oligosaccharides and Native Inulin by Infant Fecal Microbiota Attenuates Pro‐Inflammatory Responses in Immature Dendritic Cells in an Infant‐Age‐Dependent and Fructan‐Specific Way

Logtenberg

Akkerman

et al. 2020

Molecular Nutrition Food Res

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“…2‐FL has been spotlighted because of its neutraceutical and pharmaceutical potentials in industry. Recently, microbial production of 2‐FL has been attempted in some research groups because it has advantages in terms of production efficiency as compared with chemical‐ or enzymatic methods (Bych et al, ). In biosynthesis of 2‐FL using engineered E. coli , lactose is fucosylated by exogenous fucosyltransferase using guanosine 5′‐diphosphate (GDP)‐ l ‐fucose as a fucose donor (Lee et al, ).…”

mentioning

confidence: 99%

Enhanced production of 2’‐fucosyllactose from fucose by elimination of rhamnose isomerase and arabinose isomerase in engineered Escherichia coli

Jung

Chin

Lee

et al. 2019

Biotech & Bioengineering

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2′-Fucosyllactose (2-FL), one of the most abundant oligosaccharides in human milk, has been spotlighted for its neutraceutical and pharmaceutical potentials. Microbial production of 2-FL is promising since it is efficient as compared to other production methods. In 2-FL microbial production via the salvage pathway for biosynthesis of guanosine 5′-diphosphate (GDP)-L-fucose from fucose, the conversion yield from fucose is important because of the high price of fucose. In this study, deletion of the genes (araA and rhaA) coding for arabinose isomerase (AraA) and rhamnose isomerase (RhaA) was attempted in engineered Escherichia coli for improving 2-FL production by using fucose, lactose, and glycerol. The engineered E. coli constructed previously is able to express fucokinase/GDP-L-fucose pyrophosphorylase (Fkp) from Bacteroides fragilis and the α-1,2-fucosyltransferase (FucT2) from Helicobacter pylori and deficient in β-galactosidase (LacZ), fucose isomerase (FucI), and fuculose kinase (FucK). The additional double-deletion of the araA and rhaA genes in the engineered E. coli enhanced the product yield of 2-FL to 0.52 mole 2-FL/mole fucose, and hence the concentration of 2-FL reached to 47.0 g/L, which are 44% and two-fold higher than those (23.1 g/L and 0.36 mole 2-FL/mole fucose) of the control strain in fed-batch fermentation. Elimination of sugar isomerases exhibiting promiscuous activities with fucose might be critical in the microbial production of 2-FL through the salvage pathway of GDP-L-fucose.

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“… Milch‐Zusammensetzung a) Zusammensetzung der menschlichen Muttermilch im Vergleich zur Kuhmilch in g/l; b) Durchschnittliche prozentuale Verteilung von HMO (Strukturen s. Abbildungen –) (modifiziert nach ). …”

Section: Muttermilchunclassified

Mehr als 200 gute Gründe für das Stillen

Breuer¹,

Weingarten²

2019

Chemie in nserer Zeit

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Zusammenfassung Muttermilch ist eine beeindruckende „biologische Flüssigkeit“, die sich über Millionen von Jahren zu einer entscheidenden Ernährungs‐ und Immunschutzquelle für Säuglinge entwickelt hat. Die funktionalen humanen Milcholigosaccharide (HMO) der menschlichen Muttermilch sind in Struktur und Zusammensetzung weitaus komplexer als die der Milch vieler anderer Säugetierspezies. Die Forschung nach den Ursachen, warum der Mensch unter Energieeinsatz solch eine Vielfalt an HMO produziert, ist hochaktuell und hat gerade in den letzten zehn Jahren an Bedeutung gewonnen. Moderne Synthesemethoden ermöglichen den Zugang zu einer Vielzahl an HMO – auch, um die Struktur‐Aktivitäts‐Wechselwirkungen aufzuklären. Die industrielle Produktion einzelner HMO wurde bereits entwickelt, Zulassungen für die Zugabe erster HMO in Säuglingsmilchnahrungen wurden erteilt und die ersten Produkte sind auf dem Markt erhältlich. Damit wurde in den letzten zehn Jahren ein wichtiger Schritt gemacht, die Zusammensetzung moderner Säuglingsmilchnahrungen weiter an das natürliche Original anzunähern. Stillen ist dennoch nach wie vor der Goldstandard für die Babyernährung, denn es gibt mehr als 200 gute (HMO)‐Gründe für das Stillen.

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Production of HMOs using microbial hosts — from cell engineering to large scale production

Cited by 164 publications

References 41 publications

Fermentation of Chicory Fructo‐Oligosaccharides and Native Inulin by Infant Fecal Microbiota Attenuates Pro‐Inflammatory Responses in Immature Dendritic Cells in an Infant‐Age‐Dependent and Fructan‐Specific Way

Fermentation of Chicory Fructo‐Oligosaccharides and Native Inulin by Infant Fecal Microbiota Attenuates Pro‐Inflammatory Responses in Immature Dendritic Cells in an Infant‐Age‐Dependent and Fructan‐Specific Way

Enhanced production of 2’‐fucosyllactose from fucose by elimination of rhamnose isomerase and arabinose isomerase in engineered Escherichia coli

Mehr als 200 gute Gründe für das Stillen

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