Computational Systems Biology Lab

Mycolic acids, which render unique qualities to mycobacteria, are known to be important for mycobacterial growth, survival, and pathogenicity. It is of interest to understand the evolutionary origins of the mycolic acid pathway (MAP), as well as the common minimum principles critical for generating the capability of mycolic acid biosynthesis. The recent curation of a comprehensive model of the MAP in Mycobacterium tuberculosis and the availability of a large number of genome sequences make it feasible to carry out detailed sequence and phylogenetic analyses, to address these questions. A comprehensive phylogenetic pathway profile analysis was carried out for 318 fully sequenced bacterial genomes, for each of the proteins present in the MAP.

The organisms were clustered on the basis of co-occurrence of the MAP proteins in their proteome, while the proteins were clustered on the basis of their phylogenetic profiles. The MAP proteins were also searched against the nonredundant sequence database, to identify similar proteins from other phyla. The pathway profiles indicate that four proteins and certain protein domains stand out as more characteristic to mycolate producing organisms. Further analysis leads to the identification of the desaturases DesA1 and DesA2 and certain domains of Fas and Pks13 as hallmarks of the pathway. The roles of these proteins in some other organisms, as well as the distribution of these proteins across all known genome sequences are also briefly discussed.

The clustering of organisms, carried out to group organisms with similar profiles, provides a means of obtaining finer classification as compared to the standard taxonomic method. The results indicate that the MAP and hence the capacity of mycolic acid production in mycobacteria is an example of an emergent property that has come about by recruiting enzymes from unrelated pathways in plants, presumably through lateral gene transfer. The understanding of the hallmarks of mycolic acid biosynthesis will also find application in evaluating drug targets.

Original Paper:

• K. Raman, P. Rajagopalan, and N. Chandra, “Hallmarks of mycolic acid biosynthesis: A comparative genomics study,” Proteins: Structure, Function, and Bioinformatics, vol. 69, iss. 2, pp. 358-368, 2007.
  [bibtex]

  @article{Raman2007Hallmarks,
    abstract = {Mycolic acids, which render unique qualities to mycobacteria, are known to be important for mycobacterial growth, survival, and pathogenicity. It is of interest to understand the evolutionary origins of the mycolic acid pathway ({MAP}), as well as the common minimum principles critical for generating the capability of mycolic acid biosynthesis. The recent curation of a comprehensive model of the {MAP} in Mycobacterium tuberculosis and the availability of a large number of genome sequences make it feasible to carry out detailed sequence and phylogenetic analyses, to address these questions. A comprehensive phylogenetic pathway profile analysis was carried out for 318 fully sequenced bacterial genomes, for each of the proteins present in the {MAP}. The organisms were clustered on the basis of co-occurrence of the {MAP} proteins in their proteome, while the proteins were clustered on the basis of their phylogenetic profiles. The {MAP} proteins were also searched against the nonredundant sequence database, to identify similar proteins from other phyla. The pathway profiles indicate that four proteins and certain protein domains stand out as more characteristic to mycolate producing organisms. Further analysis leads to the identification of the desaturases {DesA1} and {DesA2} and certain domains of Fas and Pks13 as hallmarks of the pathway. The roles of these proteins in some other organisms, as well as the distribution of these proteins across all known genome sequences are also briefly discussed. The clustering of organisms, carried out to group organisms with similar profiles, provides a means of obtaining finer classification as compared to the standard taxonomic method. The results indicate that the {MAP} and hence the capacity of mycolic acid production in mycobacteria is an example of an emergent property that has come about by recruiting enzymes from unrelated pathways in plants, presumably through lateral gene transfer. The understanding of the hallmarks of mycolic acid biosynthesis will also find application in evaluating drug targets. Proteins 2007. {\copyright} 2007 {Wiley-Liss}, Inc.},
    added-at = {2018-12-02T16:09:07.000+0100},
    author = {Raman, Karthik and Rajagopalan, Preethi and Chandra, Nagasuma},
    doi = {10.1002/prot.21591},
    interhash = {082b9fa12e5161e2255c2454ff21f5d7},
    intrahash = {7bc667b3440d2fd8fd4027d9362f5cc6},
    issn = {1097-0134},
    journal = {Proteins: Structure, Function, and Bioinformatics},
    keywords = {comparative\_analysis mtb myown sequence\_analysis},
    number = 2,
    pages = {358--368},
    posted-at = {2012-02-07 09:25:27},
    priority = {2},
    timestamp = {2019-02-10T16:15:28.000+0100},
    title = {Hallmarks of mycolic acid biosynthesis: A comparative genomics study},
    url = {http://dx.doi.org/10.1002/prot.21591},
    volume = 69,
    year = 2007
  }