Research groupsKirschning group
Research - biotransformations (SynBio)

Mutasynthesis, a synthetic tool in natural product chemistry

The ansamitocins (maytansinoids), geldanamycin as well as rifamycin are famous members of the class of ansamycin antibiotics which all bear aminohydroxybenzoic acid (AHBA) as polyketide synthase (PKS) starting building block. 

Review: with T. Knobloch and K. Harmrolfs, C. R. Chimie 2008, 1523-1543.


Mutasynthesis is a straightforward technique, that combines the genetic manipulation of biosynthetic pathways with chemical synthesis. It requires the generation of mutants of a producer organism blocked in the formation of a biosynthetic building block of the end-product. Administration of structurally modified, so called mutasynthons to these blocked mutant reconstitutes the substrate flow. However, in these cases the structural modifications result in new metabolites.

We carried out comprehensive mutasynthetic studies with three microbial strains (Actinosynnema pretiosum, Streptomyces hygroscopicus and Amycolatopsis mediterranei) blocked in the biosynthesis of aminohydroxybezoic acid (AHBA).

Reviews: with F. Hahn, Angew. Chem. Int. Ed. 2012, 51, 4012–4022; with S. Eichner, F. Taft, T. Knobloch, K. Harmrolfs, Synlett 2012, 416-426; with F. Taft, T. Knobloch, Org. Biomol. Chem. 2007, 5, 3245-3259; with J. Franke, S. Eichner, C. Zeilinger, A. Kirschning, Nat. Prod. Rep. 2013, 30, 1299 - 1323.


Terpenes are the most diverse class of secondary metabolites. They are generated from a linear precursor - in the case of sesquiterpenes this is farnesyl pyrophosphate (FPP) - by means of a cascade reaction. We demonstrated that sesquiterpene cyclases like presilphiperfolan-8-β-ol synthase (Bot2) show good substrate flexibility which allow to create new heteroatom-modified tricyclic sesquiterpenoids as shown for Bot2. For some new terpenoids GC-O analysis revealed an ethereal, peppery and camphor-like olfactoric scent.

                                                                                   olfactoric property: ethereal, peppery and camphor

C. Oberhauser, V. Harms, K. Seidel, B. Schröder, K. Ekramzadeh, S. Beutel, S. Winkler, L. Lauterbach, J. S. Dickschat, A. Kirschning, Angew. Chem. Int. Ed. 2018, 57, 11802-11806.