Molecular genetic mining of the Aspergillus secondary metabolome: discovery of the emericellamide biosynthetic pathway.
The recently sequenced genomes of several Aspergillus species have revealed that these organisms have the potential to produce a surprisingly large range of natural products, many of which are currently unknown. We have found that A. nidulans produces emericellamide A, an antibiotic compound of mixed origins with polyketide and amino acid building blocks. Additionally, we describe the discovery of four previously unidentified, related compounds that we designate emericellamide C-F. Using recently developed gene targeting techniques, we have identified the genes involved in emericellamide biosynthesis. The emericellamide gene cluster contains one polyketide synthase and one nonribosomal peptide synthetase. From the sequences of the genes, we are able to deduce a biosynthetic pathway for the emericellamides. The identification of this biosynthetic pathway opens the door to engineering novel analogs of this structurally complex metabolite.
Chiang
Yi-Ming
YM
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Szewczyk
Edyta
E
Nayak
Tania
T
Davidson
Ashley D
AD
Sanchez
James F
JF
Lo
Hsien-Chun
HC
Ho
Wen-Yueh
WY
Simityan
Hagop
H
Kuo
Eric
E
Praseuth
Alex
A
Watanabe
Kenji
K
Oakley
Berl R
BR
Wang
Clay C C
CC
D001233:Aspergillus nidulans / Q000235:genetics / Q000378:metabolism*; D047630:Depsipeptides / Q000096:biosynthesis*; D005285:Fermentation; D018390:Gene Targeting; D005800:Genes, Fungal; D016247:Information Storage and Retrieval; D013058:Mass Spectrometry; D016366:Open Reading Frames
D047630:Depsipeptides; C519738:emericellamide A