text: Although the biosynthetic pathway of callystatin A has not been explicitly described, its polyketide structure indicates that the pathway must involve the polyketide synthase (PKS) enzyme complex. In general, in a modular fashion, an acetate starting unit in the loading module is extended by two carbons each time by the ketosynthase (KS) domain. The acyl groups are loaded onto the acyl carrier protein (ACP) with the help of the acyltransferase (AT) domain. Each module contains different combinations of the ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) domains that can modify and tailor the two-carbon subunits to form the resulting fatty acid chain. The final module contains a thioesterase (TE) domain that hydrolyzes the thioester bond to release the fatty acid chain and coenzyme A.
  In the same manner, callystatin A biosynthesis starts with an acetate unit and elongates by either the malonate or the methyl malonate extender units, depending on the specific module. An exception to this is in module 7 where an ethyl malonate molecule replaces the other two options as the extender unit. It is assumed that the stereochemistry results from the activity of the domains and the absolute configuration is specified by the overall PKS complex. After being released from the thioesterase domain as a long fatty acid chain, the characteristic α,β-unsaturated lactone moiety is formed through a lactonization step to result in the final structure.