2024年6月18日，Martin Grininger教授应吕永琴教授邀请，来到北京化工大学 进行学术合作交流，并做题为“Programming multistep biosynthesis with help of megasynthases”的学术报告。

    Professor Martin Grininger is a distinguished scientist specializing in biomolecular chemistry. He earned his doctoral degree from Ludwig Maximilians University。Following his doctoral studies, Prof. Grininger led a project group in Biological Chemistry at the Max-Planck-Institute of Biochemistry from 2006 to 2011. He also served as a visiting professor at the University of Vienna, Faculty of Chemistry, from June 2010 to January 2011. He held the prestigious W1 and W2-Lichtenberg Professorships of the Volkswagen Foundation from 2012 to 2019. Since January 2020, he has been a W2-Professor of Biomolecular Chemistry at Goethe University Frankfurt.

    The type I fatty acid (FASs) and polyketide synthases (PKSs) are up to several megadalton large multienzymes, termed megasynthases, that catalyze C-C bond forming reactions in compartmentalized space.  Compartmentalization is largely achieved by the transacylation.

function of FASs and PKSs, i.e., the enzymatic reaction responsible for selecting substrates from the bulk cytoplasm, and further relies on the specific protein architecture as well as the shuttled distribution of substrates between the enzymatic domains. Controlling the transacylation function of FASs and PKSs as well as the specificity of their C-C bond forming reactions enables the modulation of the product output of these proteins to access platform chemicals and bioactive compounds. Several examples for engineering megasynthases will be presented: We employed fungal and mammalian FASs for the custom synthesis of platform chemicals, among them short-chain fatty acids, aldehydes, alcohols, methylketones and lactones. Here, FAS constructs were mutated in the transferase and ketoacyl synthase domains to increase the complexity of the synthesized compounds. Further, we inserted the mammalian FAS transferase domain (MAT) into modular PKSs to enable the in vitro chemoenzymatic synthesis of new polyketides, including fluorinated 12- and 14-membered macrolactones with the same fluoro-methyl motif as in the next-generation antibiotic solithromycin.