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Review
. 2017 Dec 15;3(1):3-19.
doi: 10.1016/j.synbio.2017.12.001. eCollection 2018 Mar.

Simple glycolipids of microbes: Chemistry, biological activity and metabolic engineering

Ahmad Mohammad Abdel-Mawgoud  1 , Gregory Stephanopoulos  1
Affiliations
Review

Simple glycolipids of microbes: Chemistry, biological activity and metabolic engineering

Ahmad Mohammad Abdel-Mawgoud et al. Synth Syst Biotechnol. .

Abstract

Glycosylated lipids (GLs) are added-value lipid derivatives of great potential. Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents, they have diverse biological activities with promising biomedical and cosmeceutical applications. Glycolipids, especially those of microbial origin, have interesting antimicrobial, anticancer, antiparasitic as well as immunomodulatory activities. Nonetheless, GLs are hardly accessing the market because of their high cost of production. We believe that experience of metabolic engineering (ME) of microbial lipids for biofuel production can now be harnessed towards a successful synthesis of microbial GLs for biomedical and other applications. This review presents chemical groups of bacterial and fungal GLs, their biological activities, their general biosynthetic pathways and an insight on ME strategies for their production.

Keywords: Biosurfactant; Glycolipids biosynthesis; Glycosides; Glycosyl/acyl transferases; Lipid biotechnology; Physiological roles.

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Figures

Fig. 1
Fig. 1
Classification of glycolipids and main types of linkages between their glycosyl and lipid residues. (A) Simple glycolipids (SGLs) comprise glycolipids consisting of glycosyl and lipid residues only, whereas, complex glycolipids (CGLs) contain glycerol, ceramide, phenolic, peptide, nucleoside or polysaccharide residues in addition to the glycosyl and lipid residues. (B) Glycosyl and lipid residues are mainly linked via O-glycosidic and/or ester bonds, and less frequently via N-glycosidic and/or amide bonds.
Fig. 2
Fig. 2
Approximate distribution of microbial producers of simple glycolipids in different bacterial and fungal phyla. Incidences of microbial production of chemically unique SGLs in every microbial phylum were counted. Homologues or stereoisomers of the same chemically unique SGLs did not add into these calculations to avoid false overestimations. As an example, rhamnolipids (RLs) exist in two unique structures known so far, mono-rhamnolipids and di-rhamnolipids containing one and two rhamnose moieties, respectively, and are produced by proteobacterial species. Although these two RL congeners has several homologues varying in chain length of their lipid moiety, they were counted as two chemically unique SGLs in our calculations. Only the phylum of the microbial producer and not its genus and species identity that was taken into account; for example, although di-rhamnolipids are produced by different species of the genus Pseudomonas and Burkholderia, all di-rhamnolipids scored one hit in our calculations because all these di-rhamnolipids producers belong to the same phylum, Proteobacteria.
Fig. 3
Fig. 3
Structures of prototypic members of bacterial and fungal simple glycolipid (SGL) groups. The glycosyl and lipid residues are colored in red and blue, respectively. Bacterial and fungal SGLs are represented in the upper and lower halves (separated by a line) of the figure, respectively. The representative structure of fungally produced glycosylated paraconic acids (20th group of SGLs) is not given as their structures have been debated , .
Fig. 4
Fig. 4
Key enzymes of glycolipid biosynthesis and hydrolysis. Last steps of glycolipid biosynthesis involves linking of sugar and lipid moieties via either or both Acyl Transferases (AT) (A1 and A2, forward reactions) and Glycosyl Transferases (GT) (B1 and B2, forward reactions) which catalyze the ester and glycosidic bonds formation, respectively. Glycolipids are catabolized or broken down by Lipid Esterase (LE), Carbohydrate Esterases (CE) and Glycoside Hydrolases (GH) that hydrolyze the bond between alkyl-alkanoate ester, acyl-sugar ester and glycosidic bonds, respectively (reverse reactions). L1: Coenzyme A (CoA-S-) or Acyl Carrier Protein (ACP-S-) activating groups on acyl donors; L2: Nucleotides or phosphates activating groups on glycosyl donors. R: any substitution that could be glycosyl, lipid, or glycolipid units. Notes: β-glucose and R-3-hydroxyalkanoate are used as examples of any sugar and hydroxyl fatty acid of any chain length (n), respectively. Hydrolysis reactions do not generate activated products.
Fig. 5
Fig. 5
Sugar and lipid precursors of prominent members of simple glycolipid groups and their furnishing pathways. Biosynthesis of simple glycolipids that harbor glucoside units, like glucosides of astaxanthin and zeaxanthin as well as glucosylated sterols , cellobiose and sophorose lipids , require UDP-glucose as glycosyl donor. Peculiar glycosyl donors that are activated in other ways than UDP are required in case of rhamnolipids , trehalolipids , vicenistatin and elaiophylin . All glycosyl donors are derived from glucose -1-phosphate except that of glycosylated hopanoids whose glycosyl donors is derived from β-d-fructofuranose-6-phosphate and ribose . Mannosylerythritol lipids are expected to derive the glycosyl unit, mannosylerythritol, from erythritol and GDP-mannose which originate from d-erythrose-4-phosphate and β-d-fructofuranose-6-phosphate intermediates of the pentose phosphate pathway as described in the yeast Yarrowia lipolytica, . The lipid moiety originates mostly from fatty acid synthesis and/or β-oxidation except glycosylated macrolides, carotenoids and sterols/hopanoids whose lipid moiety is furnished from the polyketide for the former and from mevalonate/isoprenoid pathway for the latter two groups. 6PGL: 6-phosphogluconolactone; 6PG: 6-phosphogluconic acid; Ru5P: d-Ribulose-5-phosphate; R5P: d-Ribose-5-phosphate; X5P: d-Xylulose-5-phosphate; S7P: d-Sedoheptulose-7-phosphate; Gly3P: D-Glyceraldehyde-3-phosphate; DHAP: Dihydroxyacetone phosphate; Ery4P: d-Erythrose-4-phosphate; Fru6P: β-d-Fructofuranose-6-phosphate; Fru1,6BP: β-d-Fructofuranose-1,6-bisphosphate; dTDP-Rha: dTDP-rhamnose; Tre6P: Trehalose-6-phosphate; Glc: d-Glucopyranose; Glc1P: Glucose-1-phosphate; Glc6P: Glucose-6-phosphate; UDP-glc: Uridine diphosphate glucose; UDP-AcGln: Uridine diphosphate N-acetylglucosamine; Man1P: Mannose-1-phosphate; GDP-Man: GDP-mannose; R-3-OH-acyl-X1: R-3-hydroxy acyl-X1 (X1 = -CoA/-ACP); X2 = Mycolyl Carrier Protein. PPP: Pentose Phosphate Pathway. Dashed lines means that multiple biosynthetic steps are involved.
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