The 1H NMR spectra and 13C NMR data of the synthesized standard matched those reported by Hoppe and Schollkopf [33]. Nucleotide sequence see more accession numbers The nucleotide sequence of the gene clusters were deposited to NCBI GenBank under the following accession numbers: KJ742064 for FS ATCC43239, JK742065 for FA UTEX1903, KJ767018 for WI HT-29-1 and KJ767017 for HW IC-52-3. The nucleotide sequence of the 16S ribosomal RNA gene was also deposited to NCBI GenBank under

the following accession numbers: KJ768872 for FS ATCC43239, KJ768871 for FA UTEX1903, KJ767016 for WI HT-29-1 and KJ767019 for HW IC-52-3. Acknowledgements We thank Prof William Gerwick for valuable discussions and Dr Paul D’Agostino for advice Smoothened Agonist datasheet and editing the manuscript. Prof. Thomas Hemscheidt and Dr Benjamin Philmus assisted with providing University of Hawaii strains. MCM and MLM thank Dr Colin Stack, check details Dr David Harman and Dr Emily Monroe for valuable discussions and help. RV, DS and BMB thank Kathryn Howard and Dr. Ormond Brathwaite for valuable discussions and BMB thanks DOE for a GAANN fellowship (2012-2013). Funding for supplies for expression work performed by MLM in LG’s laboratory was provided by NIH (NCI) CA108874. RV, DS and BMB were funded by Case Western Reserve University. MCM and MLM were funded by the University of Western Sydney

HDR Scholarship and RTS funding and the Australian Research Council, Discovery Project DP0880264. Additional files Additional file 1: BLASTx analysis of gene clusters analyzed in this study. Table S1. The wel gene cluster in Westiella intricata UH strain HT-29-1. Table S2. The wel gene cluster in Hapalosiphon welwitschii UH strain IC-52-3. Table S3. The hpi gene cluster Histidine ammonia-lyase in Fischerella sp. ATCC 43239. Table S4. The amb gene cluster in Fischerella

ambigua UTEX 1903 from this study. Table S5. The hpi gene cluster in Fischerella sp. PCC 9339. Table S6. The wel gene cluster in Fischerella sp. PCC 9431. Table S7. The wel gene cluster in Fischerella muscicola SAG 1427-1. Additional file 2: Phylogenetic analysis of HpiP1/AmbP1/WelP1 enzyme. Additional file 3: Sequence alignment and identification of conserved motifs from isonitrile proteins I1and I2. Additional file 4: Sequence alignment of isonitrile protein I3 with IsnB and PvcB. Additional file 5: 1 H and 13 C NMR and HRMS spectra for chemically synthesized cis and trans indole-isonitriles. Additional file 6: LC-ESI-MS spectrum for enzyme-catalyzed indole-isonitrile biosynthesis product. Additional file 7: HRESI-MS and MS peaks from LC-MS spectra for chemically synthesized indole-isonitrile and cyanobacterial extracts from FS ATCC43239 and FA UTEX1903. Additional file 8: Sequence identity of all oxygenase proteins. Additional file 9: Sequence alignment and identification of motifs from Reiske-type oxygenases.