IUBMB Enzyme Nomenclature


Accepted name: hapalindole U synthase

Reaction: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole = hapalindole U

For diagram of reaction click here

Glossary: hapalindole U = (6aS,9R,10R,10aS)-10-isocyano-6,6,9-trimethyl-9-vinyl-2,6,6a,7,8,9,10,10a-octahydronaphtho[1,2,3-cd]indole

Other name(s): ambU1/ambU4 (gene names); famC4/famC1 (gene names)

Systematic name: 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole cyclase (hapalindole U-forming)

Comments: Requires Ca2+. The enzyme, which belongs to the Stig cyclases, has been characterized from multiple species of the cyanobacterial genera Fischerella and Westiellopsis. Stig cyclases catalyse a three step process including a Cope rearrangement, 6-exo-trig cyclization and electrophilic aromatic substitution. The enzyme is a heterodimer of two different proteins (AmbU1 and AmbU4). On their own, AmbU1 catalyses a different reaction, producing 12-epi-hapalindole U (cf. EC, 12-epi-hapalindole U synthase) while AmbU4 appears to be inactive. Formation of hapalindole U leads to the biosynthesis of additional terpenoid indole alkaloids such as hapalindole G, ambiguine H, and ambiguine A.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:


1. Zhu, Q. and Liu, X. Discovery of a calcium-dependent enzymatic cascade for the selective assembly of hapalindole-type alkaloids: on the biosynthetic origin of hapalindole U. Angew. Chem. Int. Ed. Engl. 56 (2017) 9062-9066. [PMID: 28626997]

2. Li, S., Newmister, S.A., Lowell, A.N., Zi, J., Chappell, C.R., Yu, F., Hohlman, R.M., Orjala, J., Williams, R.M. and Sherman, D.H. Control of stereoselectivity in diverse hapalindole metabolites is mediated by cofactor-induced combinatorial pairing of stig cyclases. Angew. Chem. Int. Ed. Engl. 59 (2020) 8166-8172. [PMID: 32052896]

[EC created 2024]

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