FIG. 4.

Proposed biosynthetic scheme for MB T. (A) Region of the genome of M. tuberculosis H37Rv containing the putative MB biosynthetic enzymes. Numbering refers to chromosomal positions reported by Cole et al. (8). (B) Proposed biosynthetic cascade catalyzed by the Mbt locus. See the text for details of individual enzymatic predictions. There are significant areas of uncertainty in this model, as suggested by the following questions. (i) Does the ketoacyl synthase domain of MbtC act upon the MbtD-bound acyl carrier protein domains as shown? (ii) Does the second peptidyl/acyl carrier protein domain of MbtE function to attach the β-hydroxybutyrate as shown, or does it transfer the acyl group to the first lysine (the R₅) position in Fig. 2? (iii) Do MbtE and MbtF act in the order in which they appear in the genomic locus, or are they reversed? (iv) Is MbtG involved in N-hydroxylation as shown? (v) What is the nature of the acyltransferase, and how is the specificity determined? When does this act and upon what substrate? Since this determines the ratio of water-soluble to cell-associated siderophore, this is a critical question. (vi) What is the role played by MbtH and MbtJ?