Manipulating polyketide stereochemistry by exchange of polyketide synthase modules

A key goal of modular polyketide synthase (PKS) engineering is to alter polyketide stereochemistry. Here we report that exchanging whole PKS modules is a more productive approach than swapping individual ketoreductase (KR) domains for introducing rare 'A2' and 'B2' stereochemistry into model polyketides, and identify four modular 'biobricks' for such synthetic biology efforts. Exchange of polyketide synthase (PKS) modules by genetic engineering leads to efficient modification of polyketide stereochemistry.