The biosynthesis of galactofuranosyl residues in galactocarolose

Abstract

1. Cell-free extracts of Penicillium charlesii G. Smith were used in a study of the biosynthesis of the galactofuranose polymer, galactocarolose. 2. UDP-glucose and UDP-galactopyranose were precursors of galactocarolose and it was shown that the galactofuranose residues in the polymer were formed from glucose without fission of the hexose carbon chain. 3. A new nucleotide, UDP-alpha-d-galactofuranose, was formed by the system and was a major product when polymer synthesis was inhibited by F(-) or Zn(2+); the nucleotide was isolated and its structure determined. 4. UDP-alpha-d-galactofuranose was efficiently utilized for polymer synthesis and shown to be formed from the pyranose nucleotides. 5. A route for the biosynthesis of galactocarolose, involving a novel ring contraction of the hexose residue while still attached to the nucleotide, is proposed.

Structure, mechanism, and dynamics of UDP-galactopyranose mutase

“…For example, galactocarolose, an extracellular β-D-(1→5)-linked polygalactofuranose produced by Penicillium charlesii , was the first polysaccharide shown to contain Gal f [1], motivating interest in the underlying biosynthetic pathway. Decades later, it was shown that P. charlesii could not use exogenous galactose to produce galactocarolose [2], leading to the discovery of a new nucleotide, UDP-Gal f , as the precursor in galactocarolose biosynthesis [3]. Similarly, investigations into the origins of Gal f in the T1 antigen of Salmonella typhimurium identified UDP-Gal p in the biosynthetic pathway and suggested the existence of an enzyme that catalyzes the 6-to-5 ring contraction of UDP-Gal p to UDP-Gal f [4, 5].…”

Synthesis of Galactofuranosides by Regioselective Ring Opening of a 1,4-Anhydrogalactopyranose Derivative: A Possible Chemical Model for an Unprecedented Enzymatic Reaction

“…[4] Fortunately, galactofuranose residues have not hitherto been identified in mammals. Uridine 5Ј-(α--galactofuranosyl pyrophosphate) (UDP-Galf) has been isolated by Trejo et al [5] from Penicillium charlesii and has been shown to act as donor in various Galf transferases. [6] UDP-Galf is formed [7,8] through an unprecedented enzymatic reaction catalyzed by UDP-galactopyranose mutase (EC 5.4.99.9), an enzyme that has recently been expressed, purified, [9,10] and crystallized.…”

Contribution of Galactofuranose to the Virulence of the Opportunistic Pathogen Aspergillus fumigatus

“…Galf is most likely incorporated into cell surface components by specific galactofuranosyltransferases that use UDPGalf as a donor. The work of Trejo and colleagues in the early 1970s already suggested the existence of an enzyme converting UDP-galactopyranose into UDP-galactofuranose involved in the biosynthesis of the fungal cell wall (48). This enzyme, named UDP-galactopyranose mutase (UGM) and encoded by the glf gene, was described first for bacteria (17,30,50) and lately for several eukaryotic pathogens, including A. fumigatus (2,5).…”