Research topic in Dr. Arakawa’s laboratory
Our group focuses on actinobacteria that produce a wide variety of secondary metabolites including antibiotics. Especially, Streptomyces species, a major group of actinobacteria, produces around 70% of the known antibiotics. Other striking features in Streptomyces are the presence of linear genome and the complex morphological differentiation like fungi. Our group performs the comprehensive and integrative analyses of secondary metabolites biosynthesis, regulatory mechanism, the genomic structure, and morphological differentiation in Streptomyces. Furthermore, we extend our research topics on isolation and structural elucidation of bioactive microbial metabolites, and structural modification through chemical synthesis and enzymatic engineering. The followings are our research topics.
(1) Analysis of
biosynthetic machinery of secondary metabolites, and their structural redesign
Secondary metabolites are synthesized by
biosynthetic enzymes (proteins) through multiple steps. Based on central dogma,
enzymes are coded by “genes”, that is, secondary metabolites production is
controlled by genes. Our group analyzes the biosynthetic machinery (genes) of
secondary metabolites, and attempts to create “unnatural” natural products
through rational redesign of biosynthetic pathway.
(2) Analysis of
signaling-molecules dependent regulatory cascade for secondary metabolite
production
Streptomyces species harbors the
signaling-molecules dependent regulatory cascade for secondary metabolite
production. Our group elucidated the main regulatory pathway for two polyketide
antibiotics, lankacidin and lankamycin, coded on a linear plasmid pSLA2-L of Streptomyces
rochei. In addition, we have elucidated the chemical structures of the
butenolide-type signaling molecules SRBs in S. rochei. We now investigate
the improvement of fermentation-titer and exploring of novel metabolites
through modification of transcriptional activators and repressors involved in
regulatory cascade in Streptomyces.
(3) Activation of
silent secondary metabolite production through metabolic engineering (“genome
mining”)
Streptomyces strains harbor over 30 secondary
metabolite gene clusters, however, they only produce few compounds (ca. 10-20%)
under normal culture conditions, suggesting that most of the biosynthetic gene
clusters for secondary metabolites (ca. 80-90%) are expressed weally or not at
all. Many efforts to activate the silent biosynthetic gene clusters are
extensively performed for natural product discovery (“genome mining”). Our
group also perform genome mining approaches through extensive metabolic
engineering.
(4) Integrative
analysis of genomic structure, secondary metabolite production, regulation, and
morphological differentiation
Streptomyces
species exhibit three distinct properties; an ability to produce a wide variety
of secondary metabolites, the linear genome, and morphological differentiation.
We investigate their integrative understanding through comparative genomics and
multiple genetic manipulations.
(5) Isolation, structural
elucidation, and biological activity of microbial metabolites
One of my interests is unique structures and
biological activity of secondary metabolites in the world. Hence, our group
performs isolation, structural elucidation, and biological activity of
microbial natural products from the culture library.
(6) Others (Creation
and functional analysis of highly functional molecules through
interdisciplinary fusion)
Our group has many collaborations with
researchers who are in different field including crystallography, computational
chemistry, materials sciences, etc. to create the highly-functional molecules.
If you have questions, please contact Dr. Kenji Arakawa. I can explain our research topics through online (Zoom, Teams, etc).
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