Journal of Biochemistry Advance Access originally published online on July 23, 2009
Journal of Biochemistry 2009 146(5):659-665; doi:10.1093/jb/mvp113
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Mycolyltransferase from Mycobacterium leprae Excludes Mycolate-containing Glycolipid Substrates
1Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University; 2Laboratory of Cell Regulation and Molecular Network, Graduate School of Biostudies; and 3Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan
To whom correspondence should be addressed. Tel: +81-75-751-4047, Fax: +81-75-752-3232, E-mail: i_matsun{at}virus.kyoto-u.ac.jp
Correspondence may also be addressed to Masahiko Sugita. Tel: +81-75-751-4028, Fax: +81-75-752-3232, E-mail: msugita{at}virus.kyoto-u.ac.jp
Received June 23, 2009; Accepted July 3, 2009
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Abstract |
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Trehalose dimycolate (TDM) is a major surface-exposed mycolyl glycolipid that contributes to the hydrophobic cell wall architecture of mycobacteria. Nevertheless, because of its potent adjuvant functions, pathogenic mycobacteria appear to have evolved an evasive maneuver to down-regulate TDM expression within the host. We have shown previously that Mycobacterium tuberculosis (M.tb) and Mycobacterium avium (M.av), replace TDM with glucose monomycolate (GMM) by borrowing host-derived glucose as an alternative substrate for the FbpA mycolyltransferase. Mycobacterium leprae (M.le), the causative microorganism of human leprosy, is also known to down-regulate TDM expression in infected tissues, but the function of its mycolyltransferases has been poorly analysed. We found that, unlike M.tb and M.av FbpA enzymes, M.av FbpA was unexpectedly inefficient in transferring 
-branched mycolates, resulting in impaired production of both TDM and GMM. Molecular modelling and mutational analysis indicated that a bulky side chain of leucine at position 130 of M.le FbpA obstructed the intramolecular tunnel that was proposed to accommodate the -branch portion of the substrates. Notably, even after a highly reductive evolution, M.le FbpA remained functional in terms of transferring unbranched acyl chains, suggesting a role that is distinct from that as a mycolyltransferase.
Key Words: glycolipid, glucose monomycolate, Mycobacterium leprae, mycolyltransferase, trehalose dimycolate
Abbreviations: Fbp, fibronectin-binding protein; GMM, glucose monomycolate; M.av, Mycobacterium avium; M.le, Mycobacterium leprae; M.tb, Mycobacterium tuberculosis; TDM, trehalose dimycolate; TMM, trehalose monomycolate
*These two authors contributed equally to this work.