Ken Izumori

d-Allulose, a stereoisomer of d-fructose, extends Caenorhabditis elegans lifespan through a dietary restriction mechanism: A new candidate dietary restriction mimetic

Dietary restriction (DR) is an effective intervention known to increase lifespan in a wide variety of organisms. DR also delays the onset of aging-associated diseases. DR mimetics, compounds that can mimic the effects of DR, have been intensively explored. d-Allulose (d-Alu), the C3-epimer of d-fructose, is a rare sugar that has various health benefits, including anti-hyperglycemia and anti-obesity effects. Here, we report that d-Alu increased the lifespan of Caenorhabditis elegans both under monoxenic and axenic culture conditions. d-Alu did not further extend the lifespan of the long-lived DR model eat-2 mutant, strongly indicating that the effect is related to DR. However, d-Alu did not reduce the food intake of wild-type C.xa0elegans. To explore the mechanisms of the d-Alu longevity effect, we examined the lifespan of d-Alu-treated mutants deficient for nutrient sensing pathway-related genes daf-16, sir-2.1, aak-2, and skn-1. As a result, d-Alu increased the lifespan of the daf-16, sir-2.1, and skn-1 mutants, but not the aak-2 mutant, indicating that the lifespan extension was dependent on the energy sensor, AMP-activated protein kinase (AMPK). d-Alu also enhanced the mRNA expression and enzyme activities of superoxide dismutase (SOD) and catalase. From these findings, we conclude that d-Alu extends lifespan by increasing oxidative stress resistance through a DR mechanism, making it a candidate DR mimetic.

6-Deoxyhexoses from l-Rhamnose in the Search for Inducers of the Rhamnose Operon: Synergy of Chemistry and Biotechnology.

In the search for alternative non-metabolizable inducers in the l-rhamnose promoter system, the synthesis of fifteen 6-deoxyhexoses from l-rhamnose demonstrates the value of synergy between biotechnology and chemistry. The readily available 2,3-acetonide of rhamnonolactone allows inversion of configuration at C4 and/or C5 of rhamnose to give 6-deoxy-d-allose, 6-deoxy-d-gulose and 6-deoxy-l-talose. Highly crystalline 3,5-benzylidene rhamnonolactone gives easy access to l-quinovose (6-deoxy-l-glucose), l-olivose and rhamnose analogue with C2 azido, amino and acetamido substituents. Electrophilic fluorination of rhamnal gives a mixture of 2-deoxy-2-fluoro-l-rhamnose and 2-deoxy-2-fluoro-l-quinovose. Biotechnology provides access to 6-deoxy-l-altrose and 1-deoxy-l-fructose.

A possibility of rare sugar applications for agro-usages

単糖とは一般的にブドウ糖(D-glucose)と果糖(D-fructose) を指すことが多く,これらを中心としたいくつかの糖で,自 然界の単糖の大部分が占められている.これに対して,その 存在量が極めて少ない単糖を「希少糖」と呼ぶ.希少糖の定 義は,国際希少糖学会によって「自然界にその存在量が少な い単糖とその誘導体」とされ,単糖と糖アルコールを合わせ ると,60種弱がこれまでに知られている.さらに,これら の各種誘導体を加えていくとその数は無数になるが,希少糖 の生産手法は限られていたため,希少糖のほとんどはこれま で長く入手できない状況にあった. しかしながら,1994年に香川大学農学部の何森らの研究 グループが,D-fructoseをD-allulose(=D-psicose)に変換 する酵素を生産する微生物の単離に成功し,希少糖生産へ の扉が大きく開かれた .何森らは,この酵素(D-tagatose 3-epimerase, DTE)を用いて,希少糖であるD-alluloseの大 量生産技術の確立を進め,さらに各種希少糖を体系的に生産 するために,単糖の構造と酵素反応・有機反応をベースとし た生産の設計図を模式化した「イズモリング(Izumoring)」 (図1)を発表した .これにより,何森を中心とした香川 DOI: 10.1584/jpestics.W17-35