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Beilstein J Org Chem. 2017 Jun 21;13:1204-1211. doi: 10.3762/bjoc.13.119. eCollection 2017.

Strategies in megasynthase engineering - fatty acid synthases (FAS) as model proteins.

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Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence for Macromolecular Complexes, Goethe University Frankfurt, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany.


Megasynthases are large multienzyme proteins that produce a plethora of important natural compounds by catalyzing the successive condensation and modification of precursor units. Within the class of megasynthases, polyketide synthases (PKS) are responsible for the production of a large spectrum of bioactive polyketides (PK), which have frequently found their way into therapeutic applications. Rational engineering approaches have been performed during the last 25 years that seek to employ the "assembly-line synthetic concept" of megasynthases in order to deliver new bioactive compounds. Here, we highlight PKS engineering strategies in the light of the newly emerging structural information on megasynthases, and argue that fatty acid synthases (FAS) are and will be valuable objects for further developing this field.


fatty acid synthases; megasynthases; metabolic enzyme engineering; polyketide synthases; protein design

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