The first step involves the loading of a malonyl unit onto a discrete BryU ACP-d within an initial BryA module. The extended BryU product in BryA is then loaded onto a cysteine sidechain of BryR for interaction with ACP-a. Upon interaction, BryR then catalyzes β-Branching, facilitating an aldol reaction between the alpha-carbon of the BryU unit and the β-ketone of ACP-a, yielding a product similar to HMGS products in primary metabolism. After β-Branching, subsequent dehydration by a BryT enoyl-CoA hydratase homolog (ECH), as well as BryA O-methylation and BryB double bond isomerization of the generated HMGS product, are carried out in specific domains of the bry cluster. These post-β-Branching steps generate the vinyl methylester moieties which are found in all natural product bryostatins. Finally, BryC and BryD are responsible for further extension, pyran ring closure, and cyclization of the HMGS product to produce the novel bryostatin product.