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FUNCTIONAL IMPLICATIONS OF MULTIPLE FadD PROTEINS IN THE BIOLOGY OF MYCOBACTERIUM TUBERCULOSIS
Author(s) -
Arora Pooja,
Trivedi Omita Ashit,
Mohanty Debasisa,
Gokhale Rajesh Sudhir
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a477-a
Subject(s) - fadd , mycobacterium tuberculosis , biology , biochemistry , acyl carrier protein , ubiquitin ligase , dna ligase , ubiquitin , gene , tuberculosis , biosynthesis , medicine , pathology , apoptosis , programmed cell death , caspase
Mycobacterium tuberculosis H37Rv genome sequencing revealed an unanticipated variety of genes homologous to proteins involved in β‐oxidation machinery. Identification of 34 fadD homologous was quite remarkable and it was tempting to speculate that many of these might not even be expressed in mycobacterial lifecycle. Based on the biochemical function of mycobacterial fadD proteins, we have revealed that there are atleast two distinct families of fadD enzymes. Fatty acyl‐AMP ligase (FAAL) activates fatty acids as fatty acyl‐adenylates while Fatty acyl‐CoA ligase (FACL) activates fatty acids to fatty acyl‐CoA thioester analogues. Furthermore, we have demonstrated that FAAL directly transfer fatty acids to cognate polyketide synthase modules to produce complex lipids which are hallmarks of mycobacteria. Recent genome‐wide expression studies have emphasized the functional significance of FadD proteins under different conditions. Since these proteins play an important role in mycobacterial biology, we have designed specific inhibitors that may be further developed as antimycobacterial agents. This work was supported by grants from DBT, India to National Institute of Immunology, CSIR to PA and Wellcome Trust International Senior Research Fellowship to RSG.