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The fumagillin biosynthetic gene cluster in Aspergillus fumigatus encodes a cryptic terpene cyclase involved in the formation of ?-trans-bergamotene.

ABSTRACT: Fumagillin 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 ?-trans-bergamotene synthase in A. fumigatus as a membrane-bound terpene cyclase.

SUBMITTER: Lin HC

PROVIDER: S-EPMC3652892 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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The fumagillin biosynthetic gene cluster in Aspergillus fumigatus encodes a cryptic terpene cyclase involved in the formation of β-trans-bergamotene.

Lin Hsiao-Ching HC Chooi Yit-Heng YH Dhingra Sourabh S Xu Wei W Calvo Ana M AM Tang Yi Y

Journal of the American Chemical Society 20130319 12

Fumagillin 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]

PMID: 23488861

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