@article{5670d19280d24d25aae021cca5cf1335,
title = "Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria",
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.",
author = "Trivedi, {Omita A.} and Pooja Arora and Vijayalakshmi Sridharan and Rashmi Tickoo and Debasisa Mohanty and Gokhale, {Rajesh S.}",
note = "Funding Information: Acknowledgements We thank A.-M. Voie for embryo injections for transgenesis, S. Curado for the oskA87, Nanos-Gal4:VP16 recombinant stock, A. Cyrklaff for the oskar in situ probe, P. R{\o}rth for the pCog-Gal4:VP16 driver, D. St Johnston for anti-Staufen antibody, and members of the Ephrussi laboratory, V. Hachet and E. Izaurralde for advice and comments on the manuscript. O.H. was supported in part by a predoctoral {\textquoteleft}allocation de recherche{\textquoteright} from the French government. Funding Information: Acknowledgements We thank members of the MacKinnon lab, S. Darst, N. Opalka and D. Stokes for helpful discussions. This work was supported by grants from the NIH to D.N.W. and R.M. R.M is an investigator in the Howard Hughes Medical Institute. Funding Information: Acknowledgements The authors thank S. K. Basu for discussions. P.A. is a Senior Research Fellow of CSIR, India. R.S.G is a Wellcome Trust International Senior Research Fellow in India. This work was also supported by grants to the National Institute of Immunology by DBT, India.",
year = "2004",
month = mar,
day = "25",
doi = "10.1038/nature02384",
language = "English (US)",
volume = "428",
pages = "441--445",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6981",
}
