Discovery and Heterologous Biosynthesis of the Burnettramic Acids: Rare PKS-NRPS-Derived Bolaamphiphilic Pyrrolizidinediones from an Australian Fungus, Aspergillus burnettii

Hang Li; Cameron L M Gilchrist; Heather J Lacey; Andrew Crombie; Daniel Vuong; John I Pitt; Ernest Lacey; Yit-Heng Chooi; Andrew M Piggott

doi:10.1021/acs.orglett.8b04042

Discovery and Heterologous Biosynthesis of the Burnettramic Acids: Rare PKS-NRPS-Derived Bolaamphiphilic Pyrrolizidinediones from an Australian Fungus, Aspergillus burnettii

Org Lett. 2019 Mar 1;21(5):1287-1291. doi: 10.1021/acs.orglett.8b04042. Epub 2019 Feb 8.

Authors

Hang Li¹, Cameron L M Gilchrist¹, Heather J Lacey², Andrew Crombie², Daniel Vuong², John I Pitt³, Ernest Lacey^{2

4}, Yit-Heng Chooi¹, Andrew M Piggott⁴

Affiliations

¹ School of Molecular Sciences , The University of Western Australia , Perth , Western Australia 6009 , Australia.
² Microbial Screening Technologies Pty. Ltd. , Smithfield , New South Wales 2164 , Australia.
³ Commonwealth Scientific and Industrial Research Organisation , North Ryde , New South Wales 2113 , Australia.
⁴ Department of Molecular Sciences , Macquarie University , Sydney , New South Wales 2109 , Australia.

PMID: 30735051
DOI: 10.1021/acs.orglett.8b04042

Abstract

The burnettramic acids are a new class of antibiotics from an Australian fungus Aspergillus burnettii. The rare bolaamphiphilic scaffold consists of β-d-mannose linked to a pyrrolizidinedione unit via a 26-carbon chain. The most abundant metabolite displayed potent in vitro antifungal activity. Comparative genomics identified the hybrid PKS-NRPS bua gene cluster, which was verified by heterologous pathway reconstitution in Aspergillus nidulans.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / biosynthesis
Anti-Bacterial Agents / chemical synthesis*
Aspergillus / chemistry*
Aspergillus / metabolism
Australia
Heterocyclic Compounds, 2-Ring / chemistry*
Isomerism
Mannose / chemistry
Molecular Structure
Multigene Family
Oxidation-Reduction
Pyrrolidines / chemistry
Secondary Metabolism

Substances

Anti-Bacterial Agents
Heterocyclic Compounds, 2-Ring
Pyrrolidines
Mannose