ja312503y_si_001.pdf (2.32 MB)
The Fumagillin Biosynthetic Gene Cluster in Aspergillus fumigatus Encodes a Cryptic Terpene Cyclase Involved in the Formation of β-trans-Bergamotene
journal contribution
posted on 2013-03-27, 00:00 authored by Hsiao-Ching Lin, Yit-Heng Chooi, Sourabh Dhingra, Wei Xu, Ana M. Calvo, Yi TangFumagillin 1 is a meroterpenoid from Aspergillus
fumigatus that is known for its anti-angiogenic activity
by binding to human methionine aminopeptidase 2. The genetic and molecular
basis for biosynthesis of 1 had been an enigma despite
the availability of the A. fumigatus genome sequence.
Here, we report the identification and verification of the fma gene cluster, followed by characterization of the polyketide
synthase and acyltransferase involved in biosynthesis of the dioic
acid portion of 1. More significantly, we uncovered the
elusive β-trans-bergamotene synthase in A. fumigatus as a membrane-bound terpene cyclase.