Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria

Omita A. Trivedi, Pooja Arora, Vijayalakshmi Sridharan, Rashmi Tickoo, Debasisa Mohanty, Rajesh S. Gokhale

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

The metabolic repertoire in nature is augmented by generating hybrid metabolites from a limited set of gene products. In mycobacteria, several unique complex lipids are produced by the combined action of fatty acid synthases and polyketide synthases (PKSs), although it is not clear how the covalently sequestered biosynthetic intermediates are transferred from one enzymatic complex to another. Here we show that some of the 36 annotated fadD genes, located adjacent to the PKS genes in the Mycobacterium tuberculosis genome, constitute a new class of long-chain fatty acyl-AMP ligases (FAALs). These proteins activate long-chain fatty acids as acyl-adenylates, which are then transferred to the multifunctional PKSs for further chain extension. This mode of activation and transfer of fatty acids is contrary to the previously described universal mechanism involving the formation of acyl-coenzyme A thioesters. Similar mechanisms may operate in the biosynthesis of other lipid-containing metabolites and could have implications in engineering novel hybrid products.

Original languageEnglish (US)
Pages (from-to)441-445
Number of pages5
JournalNature
Volume428
Issue number6981
DOIs
StatePublished - Mar 25 2004
Externally publishedYes

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Polyketide Synthases
Mycobacterium
Fatty Acids
Genes
Lipids
Fatty Acid Synthases
Acyl Coenzyme A
Adenosine Monophosphate
Ligases
Mycobacterium tuberculosis
Genome
Proteins

ASJC Scopus subject areas

  • General

Cite this

Trivedi, O. A., Arora, P., Sridharan, V., Tickoo, R., Mohanty, D., & Gokhale, R. S. (2004). Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. Nature, 428(6981), 441-445. https://doi.org/10.1038/nature02384

Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. / Trivedi, Omita A.; Arora, Pooja; Sridharan, Vijayalakshmi; Tickoo, Rashmi; Mohanty, Debasisa; Gokhale, Rajesh S.

In: Nature, Vol. 428, No. 6981, 25.03.2004, p. 441-445.

Research output: Contribution to journalArticle

Trivedi, OA, Arora, P, Sridharan, V, Tickoo, R, Mohanty, D & Gokhale, RS 2004, 'Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria', Nature, vol. 428, no. 6981, pp. 441-445. https://doi.org/10.1038/nature02384
Trivedi OA, Arora P, Sridharan V, Tickoo R, Mohanty D, Gokhale RS. Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. Nature. 2004 Mar 25;428(6981):441-445. https://doi.org/10.1038/nature02384
Trivedi, Omita A. ; Arora, Pooja ; Sridharan, Vijayalakshmi ; Tickoo, Rashmi ; Mohanty, Debasisa ; Gokhale, Rajesh S. / Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. In: Nature. 2004 ; Vol. 428, No. 6981. pp. 441-445.
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