Two Separate Gene Clusters Encode the Biosynthetic Pathway for the Meroterpenoids Austinol and Dehydroaustinol in Aspergillus nidulans

Meroterpenoids are a class of fungal natural products that are produced from polyketide and terpenoid precursors. An understanding of meroterpenoid biosynthesis at the genetic level should facilitate engineering of second-generation molecules and increasing production of first-generation compounds....

Full description

Saved in:
Bibliographic Details
Published inJournal of the American Chemical Society Vol. 134; no. 10; pp. 4709 - 4720
Main Authors Lo, Hsien-Chun, Entwistle, Ruth, Guo, Chun-Jun, Ahuja, Manmeet, Szewczyk, Edyta, Hung, Jui-Hsiang, Chiang, Yi-Ming, Oakley, Berl R, Wang, Clay C. C
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 14.03.2012
Amer Chemical Soc
Subjects
Aspergillus nidulans - genetics
Aspergillus nidulans - metabolism
Biocatalysis
Chemistry
Chemistry, Multidisciplinary
Chromatography, High Pressure Liquid
Dimethylallyltranstransferase - metabolism
Gene Deletion
Genes, Fungal
Multigene Family
Mutation
Open Reading Frames
Physical Sciences
Science & Technology
Terpenes - metabolism
USTUS
METABOLITES
EFFLUX PUMP
TRANSPORTER
FUNGUS
MELIA-AZEDARACH
POLYKETIDE
CERCOSPORIN
PENICILLIUM SP
IDENTIFICATION
Online AccessGet full text

Cover

More Information
Summary:Meroterpenoids are a class of fungal natural products that are produced from polyketide and terpenoid precursors. An understanding of meroterpenoid biosynthesis at the genetic level should facilitate engineering of second-generation molecules and increasing production of first-generation compounds. The filamentous fungus Aspergillus nidulans has previously been found to produce two meroterpenoids, austinol and dehydroaustinol. Using targeted deletions that we created, we have determined that, surprisingly, two separate gene clusters are required for meroterpenoid biosynthesis. One is a cluster of four genes including a polyketide synthase gene, ausA. The second is a cluster of 10 additional genes including a prenyltransferase gene, ausN, located on a separate chromosome. Chemical analysis of mutant extracts enabled us to isolate 3,5-dimethylorsellinic acid and 10 additional meroterpenoids that are either intermediates or shunt products from the biosynthetic pathway. Six of them were identified as novel meroterpenoids in this study. Our data, in aggregate, allow us to propose a complete biosynthetic pathway for the A. nidulans meroterpenoids.
Bibliography:NIH RePORTER
ISSN:0002-7863
1520-5126
DOI:10.1021/ja209809t