Identification and Characterization of a Welwitindolinone Alkaloid Biosynthetic Gene Cluster in the Stigonematalean Cyanobacterium Hapalosiphon welwitschii

Abstract

The electrochemical cathodic reduction of cyclic imides (maleimides) to succinimides can be achieved chemoselectively in the presence of alkene, alkyne, and benzyl groups. The efficiency of the system was demonstrated by using a 3D electrode in a continuous flow reactor. The reduction of 3,4‐dimethylmaleimides to the corresponding succinimides proceeds with a 3:2 diastereomeric ratio, which is independent of the nitrogen substituent and electrode surface area. The stereoselectivity of the process was rationalized by using DFT calculations, involving an acid‐catalyzed tautomerization of a half‐enol occurring through a double hydrogen‐transfer mechanism.

Natural Product Biosynthetic Diversity and Comparative Genomics of the Cyanobacteria

“…In vitro characterization of enzymes responsible for 3-((Z)-2 0 -isocyanoethenyl) indole and geranyl pyrophosphate biosynthesis and a C-2 indole dimethylallyltransferase confirmed the assignment of the pathway and allowed a proposal for the biosynthesis of these compounds [52]. A related cluster could be assigned to the biosynthesis of welwitindolinone in Hapalosiphon welwitschii [53]. Structural diversity within the hapalindole family is generated by different types of terpene cyclizations, chlorination, methylation, and oxygenation, and further prenylation as suggested by genome sequencing efforts and bioinformatic comparison of stigonematalean strains producing diverse types of hapalindoles [54].…”

Specific Enzymatic Halogenation—From the Discovery of Halogenated Enzymes to Their Applications In Vitro and In Vivo

“…[10,16,18,40,42,45] If the halogenase is involved in nonribosomal peptide or polyketide biosynthesis,i ti se xtremely unlikely that the halogenase substrate is af ree molecule.T his would only be the case if halogenation were the first step before activation of the amino acid for peptide synthesis or the starter unit for polyketide synthesis.T hus,i ti sn ot surprising that in abiosynthetic pathway,such as the one for welwitindolinone, which does not involve any peptidyl or acyl carrier proteins, [65] halogenation occurs at af ree substrate.1 2-epi-Fischerindole U( Scheme 11) and 12-epi-hapalindole Ca re chlorinated by the non-heme-iron halogenase WelO5. [10,16,18,40,42,45] If the halogenase is involved in nonribosomal peptide or polyketide biosynthesis,i ti se xtremely unlikely that the halogenase substrate is af ree molecule.T his would only be the case if halogenation were the first step before activation of the amino acid for peptide synthesis or the starter unit for polyketide synthesis.T hus,i ti sn ot surprising that in abiosynthetic pathway,such as the one for welwitindolinone, which does not involve any peptidyl or acyl carrier proteins, [65] halogenation occurs at af ree substrate.1 2-epi-Fischerindole U( Scheme 11) and 12-epi-hapalindole Ca re chlorinated by the non-heme-iron halogenase WelO5.…”

Structural basis for halogenation by iron- and 2-oxo-glutarate-dependent enzyme WelO5

“…1a) 25,26 . This enzymatic transformation constitutes the first step in the oxidative maturation of 1 to welwitindolinones in stigonematalean cyanobacterium Hapalosiphon welwischii UTEX B1830.…”