Biotechnological production of fucosylated human milk oligosaccharides: Prokaryotic fucosyltransferases and their use in biocatalytic cascades or whole cell conversion systems.

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Human milk oligosaccharides (HMOs) constitute a class of complex carbohydrates unique to mother's milk and are strongly correlated to the health benefits of breastfeeding in infants. HMOs are important as functional ingredients of advanced infant formula and have attracted broad interest for use in health-related human nutrition. About 50% of the HMOs structures contain l-fucosyl residues, which are introduced into nascent oligosaccharides by enzymatic transfer from GDP-l-fucose. To overcome limitation in the current availability of fucosylated HMOs, biotechnological approaches for their production have been developed. Functional expression of the fucosyltransferase(s) and effective supply of GDP-l-fucose, respectively, are both bottlenecks of the biocatalytic routes of synthesis. Strategies of in vitro and in vivo production of fucosylated HMOs are reviewed here. Besides metabolic engineering for enhanced HMO production in whole cells, the focus is on the characteristics and the heterologous overexpression of prokaryotic α1,2- and α1,3/4-fucosyltransferases. Up to 20g/L of fucosylated HMOs were obtained in optimized production systems. Optimized expression enabled recovery of purified fucosyltransferases in a yield of up to 45mg/L culture for α1,2-fucosyltransferases and of up to 200mg protein/L culture for α1,3/4-fucosyltransferases.
Original languageEnglish
Pages (from-to)61-83
Number of pages23
JournalJournal of Biotechnology
Volume235
Publication statusPublished - 1 Apr 2016

Fingerprint

Fucosyltransferases
Oligosaccharides
Human Milk
galactoside 3-fucosyltransferase
Guanosine Diphosphate Fucose
Fucose
Health
Metabolic engineering
Metabolic Engineering
Infant Formula
Insurance Benefits
Carbohydrates
Nutrition
Breast Feeding
Milk
Mothers
Availability
Proteins
Recovery

Keywords

  • human milk oligosaccharides
  • fucosyllactose
  • fucosyltransferases
  • multienzyme cascade
  • whole cell systems
  • metabolic engineering

Fields of Expertise

  • Human- & Biotechnology

Treatment code (Nähere Zuordnung)

  • Review

Cite this

@article{496f900f89c94ed49c832b415c2d4ec9,
title = "Biotechnological production of fucosylated human milk oligosaccharides: Prokaryotic fucosyltransferases and their use in biocatalytic cascades or whole cell conversion systems.",
abstract = "Human milk oligosaccharides (HMOs) constitute a class of complex carbohydrates unique to mother's milk and are strongly correlated to the health benefits of breastfeeding in infants. HMOs are important as functional ingredients of advanced infant formula and have attracted broad interest for use in health-related human nutrition. About 50{\%} of the HMOs structures contain l-fucosyl residues, which are introduced into nascent oligosaccharides by enzymatic transfer from GDP-l-fucose. To overcome limitation in the current availability of fucosylated HMOs, biotechnological approaches for their production have been developed. Functional expression of the fucosyltransferase(s) and effective supply of GDP-l-fucose, respectively, are both bottlenecks of the biocatalytic routes of synthesis. Strategies of in vitro and in vivo production of fucosylated HMOs are reviewed here. Besides metabolic engineering for enhanced HMO production in whole cells, the focus is on the characteristics and the heterologous overexpression of prokaryotic α1,2- and α1,3/4-fucosyltransferases. Up to 20g/L of fucosylated HMOs were obtained in optimized production systems. Optimized expression enabled recovery of purified fucosyltransferases in a yield of up to 45mg/L culture for α1,2-fucosyltransferases and of up to 200mg protein/L culture for α1,3/4-fucosyltransferases.",
keywords = "human milk oligosaccharides, fucosyllactose, fucosyltransferases, multienzyme cascade, whole cell systems, metabolic engineering",
author = "Barbara Petschacher and Bernd Nidetzky",
year = "2016",
month = "4",
day = "1",
language = "English",
volume = "235",
pages = "61--83",
journal = "Journal of Biotechnology",
issn = "0168-1656",
publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Biotechnological production of fucosylated human milk oligosaccharides: Prokaryotic fucosyltransferases and their use in biocatalytic cascades or whole cell conversion systems.

AU - Petschacher, Barbara

AU - Nidetzky, Bernd

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Human milk oligosaccharides (HMOs) constitute a class of complex carbohydrates unique to mother's milk and are strongly correlated to the health benefits of breastfeeding in infants. HMOs are important as functional ingredients of advanced infant formula and have attracted broad interest for use in health-related human nutrition. About 50% of the HMOs structures contain l-fucosyl residues, which are introduced into nascent oligosaccharides by enzymatic transfer from GDP-l-fucose. To overcome limitation in the current availability of fucosylated HMOs, biotechnological approaches for their production have been developed. Functional expression of the fucosyltransferase(s) and effective supply of GDP-l-fucose, respectively, are both bottlenecks of the biocatalytic routes of synthesis. Strategies of in vitro and in vivo production of fucosylated HMOs are reviewed here. Besides metabolic engineering for enhanced HMO production in whole cells, the focus is on the characteristics and the heterologous overexpression of prokaryotic α1,2- and α1,3/4-fucosyltransferases. Up to 20g/L of fucosylated HMOs were obtained in optimized production systems. Optimized expression enabled recovery of purified fucosyltransferases in a yield of up to 45mg/L culture for α1,2-fucosyltransferases and of up to 200mg protein/L culture for α1,3/4-fucosyltransferases.

AB - Human milk oligosaccharides (HMOs) constitute a class of complex carbohydrates unique to mother's milk and are strongly correlated to the health benefits of breastfeeding in infants. HMOs are important as functional ingredients of advanced infant formula and have attracted broad interest for use in health-related human nutrition. About 50% of the HMOs structures contain l-fucosyl residues, which are introduced into nascent oligosaccharides by enzymatic transfer from GDP-l-fucose. To overcome limitation in the current availability of fucosylated HMOs, biotechnological approaches for their production have been developed. Functional expression of the fucosyltransferase(s) and effective supply of GDP-l-fucose, respectively, are both bottlenecks of the biocatalytic routes of synthesis. Strategies of in vitro and in vivo production of fucosylated HMOs are reviewed here. Besides metabolic engineering for enhanced HMO production in whole cells, the focus is on the characteristics and the heterologous overexpression of prokaryotic α1,2- and α1,3/4-fucosyltransferases. Up to 20g/L of fucosylated HMOs were obtained in optimized production systems. Optimized expression enabled recovery of purified fucosyltransferases in a yield of up to 45mg/L culture for α1,2-fucosyltransferases and of up to 200mg protein/L culture for α1,3/4-fucosyltransferases.

KW - human milk oligosaccharides

KW - fucosyllactose

KW - fucosyltransferases

KW - multienzyme cascade

KW - whole cell systems

KW - metabolic engineering

M3 - Article

VL - 235

SP - 61

EP - 83

JO - Journal of Biotechnology

JF - Journal of Biotechnology

SN - 0168-1656

ER -