The PIM biosynthetic pathway. AcPIM2 and AcPIM6 are dominant PIM species, while Ac2PIM2 and Ac2PIM6 are relatively minor secondary products. Other PIM species are considered as biosynthetic intermediates and may exist in lower quantities. Each step is mediated via a mannosyltransferase or an acyltransferase. While PimE mediates the fifth mannose transfer, the enzymes that mediate the third, fourth, and sixth mannose transfer have not been identified. The acyltransferase-mediating conversion of monoacyl PIMs to diacyl PIMs has not been identified (indicated by question marks). Enzymes that mediate LM/LAM biosynthesis are not shown. Ac2PIM2, diacyl phosphatidylinositol dimannoside; AcPIM2, monoacyl phosphatidylinositol dimannoside; LAM, lipoarabinomannan; LM, lipomannan; PIM, phosphatidylinositol mannoside.