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).

[Top page] [Research topic][Member] [Publication]

[Japanese page]