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15 Biosynthesis of Mycobacterial Lipids by Multifunctional Polyketide Synthases

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15 Biosynthesis of Mycobacterial Lipids by Multifunctional Polyketide Synthases, Page 1 of 2

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Abstract:

The cell envelope of mycobacterium consists of a dense network of unusual lipids and sugars. This impermeable barrier imparts resistance against hostile environments and to the commonly used antimicrobial agents. Long-chain α-alkyl β-hydroxy mycolic acids are the core lipid constituents of mycobacterial cell envelope. These are esterified to the arabinogalactan to form the mycolic arabinogalactan (MAG), which link to the peptidoglycan through a phosphodiester bond. In addition, mycolic acids also exist as free glycolipids in the form of trehalose monomycolate (TMM) and trehalose dimycolate (TDM). Other mycobacterial cell envelope lipids include sulfolipids (SL), polyacyl trehalose (PAT), mannosyl-β-1-phosphomycoketide (MPM), and diacyl trehalose (DAT), all of which require polyketide enzymatic machinery for their biosynthesis. Some polyketide derived lipids include two structurally related members, phenolphthiocerol glycolipid (PGL) and phthiocerol dimycoserosates (PDIMs), mycobacterial siderophores that are involved in iron sequestration and glycopeptidolipids (GPLs) isolated from opportunistic environmental mycobacteria. In 1998, the genome sequencing project revealed a large number of proteins homologous to polyketide synthases (PKSs) which typically produce secondary metabolites in and fungi. Polyketide synthases function as multifunctional enzymatic assembly lines. NRPS-PKS server provides novel clues about putative polyketide products of new modular PKS clusters based on comparison with sequence and structural features of PKS domains in PKSDB. Sulfolipids consist of phthioceronic acid and hydroxyphthioceronic acids acylated along with fatty acids to a sulfated trehalose core to form sulfolipids.

Citation: Natarajan V, Mohanty D, Gokhale R. 2008. 15 Biosynthesis of Mycobacterial Lipids by Multifunctional Polyketide Synthases, p 235-247. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch15

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Malonyl Coenzyme A
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Bacterial Proteins
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Fatty Acid Biosynthesis
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Figures

Image of Figure 1.
Figure 1.

Chemical structures of polyketide derived lipids from mycobacteria.

Citation: Natarajan V, Mohanty D, Gokhale R. 2008. 15 Biosynthesis of Mycobacterial Lipids by Multifunctional Polyketide Synthases, p 235-247. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch15
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Image of Figure 2.
Figure 2.

Reactions catalyzed by the essential and ancillary domains of PKS, FAS, and NRPS enzymes.

Citation: Natarajan V, Mohanty D, Gokhale R. 2008. 15 Biosynthesis of Mycobacterial Lipids by Multifunctional Polyketide Synthases, p 235-247. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch15
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Image of Figure 3.
Figure 3.

Pictorial depiction of domains predicted in genes and Mas, by PKSDB and ITERDB. The ketide units in the final PDIM structure are indicated by colors similar to the synthesizing modules.

Citation: Natarajan V, Mohanty D, Gokhale R. 2008. 15 Biosynthesis of Mycobacterial Lipids by Multifunctional Polyketide Synthases, p 235-247. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch15
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Image of Figure 4.
Figure 4.

(A) Biosynthesis of PDIM demonstrates thiotemplate-based assembly line enzymology carried out by PpsA-E, FadD26, Mas, and PapA5 proteins. (B) Mycobactin synthesis by mbt-1 and -2 clusters. mbt-1 cluster proteins synthesize the mycobactin core, and mbt-2 cluster proteins along with MbtG modify the core structure of mycobactin.

Citation: Natarajan V, Mohanty D, Gokhale R. 2008. 15 Biosynthesis of Mycobacterial Lipids by Multifunctional Polyketide Synthases, p 235-247. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch15
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Tables

Generic image for table
Table 1.

Type I polyketide synthases across various species and strains of mycobacteria

Citation: Natarajan V, Mohanty D, Gokhale R. 2008. 15 Biosynthesis of Mycobacterial Lipids by Multifunctional Polyketide Synthases, p 235-247. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch15

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