KR of module 2 of DEBS was replaced by a full set of reductive domains (DH, ER and KR) derived from module 1 of the rapamycin PKS as shown in Figure 2 FIGURE 2 There is at least one report of a whole module substitution, in which module 2 of DEBS was replaced with module 5 of the rapamycin PKS The activities of the two modules is identical, and the same erythromycin precursor (6-deoxyerythronolide B) was produced by the chimeric PKS; however, this shows the possibility of creating PKS with modules from two or even several different PKS in order to produce a multitude of new products. There is one problem with connecting heterologous modules though; there is recent evidence that the amino acid sequence between the ACP domain and the subsequent KS domain of downstream modules plays an important role in the transfer of the growing polyketide from one module to another. These regions have been labeled as “linkers” and although they have no direct catalytic role, any substitution of a linker region that is not structurally compatible with the wild-type PKS may cause poor yields of the expected product. Precursor-directed biosynthesis Using a semi-synthetic approach, a diketide intermediate may be added either in vitro or in vivo to a DEBS complex in which the activity of the first KS has been deleted. This means that the diketide will load onto the second KS (in module 2 of DEBS) and be processed all the way to the end as normal. It has been shown that this second KS is fairly nonspecific and a large variety of synthetic diketides can be accepted and subsequently fully elongated and released. However, it has also been seen that this KS is not highly tolerant of structural changes at the C2 and C3 positions, especially if the stereochemistry is altered. To date, this has been the most successful approach to making macrolides with potency equal to or greater than erythromycin. Ketoreductase replacement to alter stereospecificity In modular PKS, KR active sites catalyze stereospecific reduction of polyketides. Inversion of an alcohol stereocenter to the opposite stereoisomer is possible via replacement of a wild-type KR with a KR of the opposite specificity. This has rarely been done successfully, and only at the terminal KR of the DEBS complex. It has been theorized that changing the stereospecificity of a KR in an earlier module would also require