Deletion of a mycobacterial gene encoding a reductase leads to an altered cell wall containing β-oxo-mycolic acid analogues, and the accumulation of long-chain ketones related to mycolic acids



β-oxo fatty acid precursor, containing two oxo groups in close proximity has been shown to
result in the generation of a palmitone-like decomposition product in corynebacteria (Walker et
al., 1973). Such decomposition products would be expected to migrate similarly to the rapidly
migrating species that were observed in the extracts of the mutant strain. To confirm whether
unreduced precursors of
α, α' and epoxy mycolic acids were present in the mutant strain, cells
were pre-treated with sodium borohydride (NaBH
4). This pretreatment has little effect on
normal mycolates but results in the reduction of the
β-oxo group in putative α-alkyl, β-oxo fatty
acyl intermediates resulting in the formation of
α-alkyl, β-hydroxy products, viz. mature mycolic
acids. Thus, if the
α-alkyl, β-oxo fatty acid precursors of α, α' and epoxy mycolic acids did
exist in the mutant strain, pre-treatment with NaBH
4 would be expected to convert these
precursors into
α, α' and epoxy mycolic acids and TLC analysis of TBAH-treated, methylated
extracts from NaBH
4-pretreated ∆MSMEG4722 cells would show the presence of α, α' and
epoxy MAMEs due to the prior reduction of the
β-oxo group. When extracts of NaBH4 -
pretreated cells were analyzed by TLC, species migrating with the same
Rf values as α, a´ and
epoxy MAMEs were observed (Figure 3C). However, additional MAMEs were also present in
the extracts. Two closely migrating species had a very low
Rf value and were detected in total
mycolates strains from all strains (MAME-I; Figure 3C), while another with a
Rf value slightly
greater than
α-MAMEs was seen only in extracts from the mutant strain (MAME-II; Figure 3C).

MAME-I corresponded in chromatographic migration to two hydroxylated artefacts,
characterised previously in acid methanolysates of mycobacteria having epoxy mycolates
(Minnikin et al., 1982). Similar hydroxylated artefacts would be expected by NaBH
4 reduction
of the epoxy group in epoxy mycolates. Mass spectroscopic (MS) analysis confirmed these



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