Hokkaido University · Biochemistry, Genetics and Molecular Biology
Professor Toshiyuki Wakimoto's research lab specializes in natural product chemistry, with a focus on the isolation, structural elucidation, and total synthesis of bioactive natural compounds from marine and terrestrial sources. The lab investigates biologically active lipids, such as those from New Zealand green-lipped mussels, and complex marine natural products like surugamides and kasumigamide, often employing advanced synthetic methodologies and biosynthetic insights. A key direction involves understanding the biosynthesis of natural products through metagenomic and enzymatic studies, particularly in symbiotic systems involving sponges and actinomycetes. The lab also explores structure-activity relationships of neurotoxic and anti-inflammatory compounds, including aziridine-containing amino acids and tetramic acid derivatives.
Figures are computed from collected data and may differ slightly.
A lipid extract of Perna canaliculus (New Zealand green-lipped mussel) has reportedly displayed anti-inflammatory effects in animal models and in human controlled studies. However, the anti-inflammatory lipid components have not been investigated in detail due to the instability of the lipid extract, which has made the identification of the distinct active components a formidable task. Considering the instability of the active component, we carefully fractionated a lipid extract of Perna canalic
The cathepsin B inhibitor surugamide B (2), along with structurally related derivatives (A and C-E), has previously been isolated from the marine actinomycete Streptomyces sp. JAMM992. The biosynthetic genes are unexpectedly part of a cluster of four non-ribosomal peptide synthetase (NRPS) genes, two of which are responsible for the biosynthesis of the additional linear decapeptide surugamide F. However, the thioesterase domain required for the later stage of the biosynthesis of the cyclic pepti
Sponge metagenomes are a useful platform to mine cryptic biosynthetic gene clusters responsible for production of natural products involved in the sponge-microbe association. Since numerous sponge-derived bioactive metabolites are biosynthesized by the symbiotic bacteria, this strategy may concurrently reveal sponge-symbiont produced compounds. Accordingly, a metagenomic analysis of the Japanese marine sponge Discodermia calyx has resulted in the identification of a hybrid type I polyketide synt
Angel's wing mushroom, Pleurocybella porrigens, caused fatal acute encephalopathy in Japan in 2004. The structures of cytotoxic amino acids previously isolated from the mushroom motivated a study to prove the existence of an aziridine amino acid, pleurocybellaziridine (1), found in the mushroom. The ester forms of synthetic 1 were used to confirm that the fruiting bodies contained high amounts of 1. Furthermore, 1 showed significant toxicity towards rat oligodendrocytes. Detailed facts of import
An efficient total synthesis of aperidine was accomplished using a Rh-catalyzed C-H insertion of a cis-dihydrobenzofuran ring. To circumvent the facile epimerization of the cis-dihydrobenzofuran ring, we designed and prepared the C-H insertion precursor diazoamide by Raines' protocol. Finally, the efficient incorporation of a guanidine group and mild deprotection conditions yielded this labile natural product.
The tetramic acid (2,4-pyrrolidinedione) scaffold has been recognized as an important structural feature because of its mycotoxic, antibacterial, antiviral, and antioxidant activities. This important class of natural products is reportedly produced by the type-I polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS) hybrid megaenzyme systems. In contrast, the benzalacetone synthase (BAS) from Rheum palmatum is a structurally simple, plant-specific type-III PKS that catalyzes the one-step
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