Biosynthesis of Natural Products Through a Fungal Molecular Genetics

Ref ID: 18532

Author:

Takehito Nakazawa, Takashi Ookuma, Satoru Sugimoto, Satoshi Ichinoseki, Yasutaka Gotanda, Noriyasu Ishikawa,
Yuta Tsunematsu, Kan’ichiro Ishiuchi, Hiroshi Noguchi, Kenji Watanabe

Author address:

University of Shizuoka

Full conference title:

11 th European Conference on Fungal Genetics

Abstract:

Analysis of fungal genome sequences to date has revealed that ascomycetes possess far greater numbers of gene
clusters for biosynthesis of secondary metabolites, polyketides and peptides, than the numbers of natural products
that have been isolated from the organisms. Therefore, such cryptic secondary metabolism gene clusters are
anticipated to be a source of chemically diverse compounds. However, conventional methodologies in the field of
natural products chemistry cannot be applied in hunting of natural products synthesized by enzymes encoded in
the fungal genome as silent gene clusters. First, it is necessary to activate the gene cluster to induce biosynthesis
of the corresponding compounds. Here, we expressed a gene encoding a transcriptional regulator associated with
a target silent gene cluster to induce its natural product biosynthesis. This approach was used successfully to
produce two polyketides from Aspergillus oryzae and three from Chaetomium globosum.
Second, once mRNA can be transcribed from the target gene cluster, cDNA can be synthesized to allow transfer of
the cluster genes into budding yeast and achieve heterologous production of compounds. Here, we have
developed an innovative method for biosynthesizing bioactive molecules using an engineered Saccharomyces
cerevisiae strain as a host. We expressed five polyketide synthases and two nonribosomal peptide synthetases
from Aspergillus fumigatus, Chaetomium globosum and Coprinopsis cinerea. Subsequent detailed chemical
characterizations of the resulting natural products identified six polyketides and two peptides. The methodologies
shown in this study can be applied in acquisition of numerous natural products biosynthesized by silent/unknown
fungal secondary metabolism gene clusters.

Abstract Number: PR8.50

Conference Year: 2012

Link to conference website: http://www.ecfg.info/images/Abstract_Book_Electronic.pdf

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