To the best of our knowledge, there are no farnesylated 5,6-dimethyl benzimidazoles described from bacteria yet, so we became interested in elucidating their biosynthetic origin. The sandacrabin core unit DMB likely derives from the respective pathway that supplies this biosynthetic precursor to the cobalamin (vitamin B12) biosynthesis pathway, similar to the biosynthesis very recently described for the myxadazoles. The BluB enzyme, involved in this pathway oxidizes riboflavin to form DMB. On the other hand, DMB biosynthesis can also derive from 5-aminoimidazole ribotide, which is converted to 1Hbenzo [d]imidazole-5-ol by BzaA, D and F (see Figure ). Subsequent methylation steps are carried out by BzaC and BzaD, before the resulting 5-methoxy-1H-benzo [d]imidazole is converted to DMB by BzaE. Homologues for these enzymes can be found in the genome of S. defensii MSr10575 (see SI), which underlines the ability of the strain to synthesize DMB. Bacteria are also described to express a reversible condensation enzyme that fuses formate or other carboxylic acids to 1,2-diamino-4,5-dimethylbenzol to form 5,6-dimethylbenzimidazole. This enzyme is likely to work similarly to GTP cyclohydrolase type enzymes such as RIB1 removing a C1 unit bound to two vicinal nitrogen atoms as formate from GTP in a hydrolysis reaction (see Figure ). This reaction likely plays a key role in the biosynthesis of the DMB-derived core structures of sandacrabin A and C, that may be produced by condensation of the 1,2-diamino-4,5-dimethylbenzol moiety with farnesoic acid or acetic acid, respectively. To obtain their mature structure, the different DMB core structures would need to be substituted by an N-farnesyl transferase that transfers one farnesyl sidechain to the precursor of sandacrabin A, while transferring two farnesyl residues to each of the two DMB ring nitrogen atoms of sandacrabin B and C (see Figure ). As the biosynthetic machinery supplying the DMB precursor was found encoded in close proximity to the cobalamin biosynthesis pathway, the complete sandacrabin biosynthetic machinery is not clustered in a single BGC as it is commonly observed in PKS or NRPS BGCs. Furthermore, genes encoding prenyl transferase enzymes such as the missing Nfarnesyl transferase are not rare in myxobacteria, and as such we were unable to pinpoint the genes responsible for sandacrabin biosynthesis. An overview about putative prenyl transferases detected in the S. defensii MSr10575 genome can be found in the SI.