In vivo biocombinatorial synthesis of lipopeptides by COM domain-mediated reprogramming of the surfactin biosynthetic complex.
The intermolecular communication within NRPS complexes relies on the coordinated interplay of donor and acceptor communication-mediating (COM) domains. In this study, the potential of COM domains was exploited in vivo by establishing a system for the true biocombinatorial synthesis of lipopeptides via directed reprogramming of a natural NRP biosynthetic assembly line (i.e., surfactin). By means of COM domain swapping, these experiments verified the decisive role of COM domains for the control of protein-protein interactions between NRPSs, demonstrated the functionality of COM domain pairs even in the context of a heterologous host and NRPS system, and allowed for the intended skipping of a biosynthetic enzyme within a multienzymatic biosynthetic complex. Ultimately, abrogation of the selectivity barrier provided by COM domains afforded the successful simultaneous, biocombinatorial synthesis of distinct lipopeptide products.
Chiocchini
Claudia
C
Philipps-University Marburg, Faculty of Chemistry/Biochemistry, Hans-Meerwein-Strasse, D-35032 Marburg, Germany.
Linne
Uwe
U
Stachelhaus
Torsten
T
D001412:Bacillus subtilis / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D055666:Lipopeptides; D008074:Lipoproteins / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology; D008968:Molecular Conformation; D010452:Peptide Biosynthesis; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D013329:Structure-Activity Relationship
D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; C009365:surfactin peptide; D010453:Peptide Synthases