1887

Abstract

The methyl-branched fatty acyl components of sulfolipid-I (SL-I), a major glycolipid of the human pathogen , are synthesized by the polyketide synthase Pks2. (), located downstream of , encodes a protein that belongs to a subfamily of acyltransferases associated with mycobacterial polyketide synthases [polyketide synthase-associated proteins (PAPs)]. The presence of a conserved acyltransferase motif (HXDXY) suggested a role for PapA1 in acylation of sulfated trehalose to form SL-I. Targeted deletion of the H37Rv resulted in loss of SL-I, demonstrating its role in mycobacterial sulfolipid biosynthesis. Furthermore, SL-I synthesis was restored in the mutant strain following complementation with , but not with mutant alleles of containing alterations of key residues in the acyltransferase motif, confirming that PapA1 was an acyltransferase. While other clusters are associated with a single PAP-encoding gene, it was demonstrated that another open reading frame, (), located 5.8 kb downstream of is also an acyltransferase gene involved in SL-I biosynthesis: deletion of abolished SL-I production. The absence of any partially acylated intermediates in either null mutant indicated that both PapA1 and PapA2 were required for all acylation steps of SL-I assembly.

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2007-02-01
2019-11-12
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