module via a covalent acyl-AT intermediate. The importance of the AT to the stringent incorporation of specific extender unit in the synthesis of polyketide building blocks makes it vital that the mechanism and structure of these domains be well-elucidated in order to develop efficient strategies for the regiospecific engineering of extender unit incorporation in polyketide biosynthesis. Acyl Carrier Protein The ACP is not substrate specific, which allows for the interaction with every domain present within its module. This protein collaborates with the ketosynthase (KS) domain of the same module to catalyze polyketide chain elongation, and subsequently engages with the KS domain of the next module to facilitate forward chain transfer. The ACP first accepts the extender unit from the AT, then collaborates with the KS domain in chain elongation, and finally anchors the newly elongated chain as it undergoes modification at the β-keto position. In order to carry out their function, the ACP domains require post-translational addition of a phosphopantetheine group to a conserved serine residue of the ACP. The terminal sulfhydryl group of the phosphopantetheine is the site of attachment of the growing polyketide chain. Thioesterase Located at the C-terminus site of the furthest downstream module. It is terminated in a thioesterase, which releases the mature polyketide (either as the free acid or a cyclized product), via lactonization. Note: As stated above, the first module of DEBS contains an additional acyltransferase and ACP for initiation of the reactions Non-essential components Additional components, may have any one or a combination of the following: Ketoreductase- Uses NADPH to stereospecifically reduce it to a hydroxyl group Dehydratase- Catalyzes the removal of the hydroxyl group to create a double bond from organic compounds in the form of water Enolreductase- Utilizes NADPH to reduce the double bond from the organic compound Comparison between fatty acid synthesis and polyketide synthesis Fatty acid synthesis in most prokaryotes occurs by a type II synthase made of many enzymes located in the cytoplasm that can be separated. However, some bacteria such as Mycobacterium smegmatis as well as mammals and yeast use a type I synthase which is a large multifunctional protein similar to the synthase used for polyketide synthesis. This Type I synthase includes discrete domains on which individual reactions are catalyzed. In both fatty acid synthesis and polyketide synthesis, the intermediates are covalently bound to ACP, or acyl carrier protein. However, in fatty acid synthesis the original