ENTERPRISE FUTURE
O-ta & G-ko’s surprise visit
O-ta & G-ko
  • Bio & Chemicals Team Energy Technology Laboratories Taku Nishimura
  • Bio & Chemicals Team Energy Technology Laboratories Asuka Hannya
  • Senior Researcher Energy Technology Laboratories Jun Tsubota
  • O-ta An intellectually curious, energetic but gentle, simple-hearted dog
  • G-ko An eco-friendly, energy-saving and convenience-loving cat

What are ketone bodies, these “good-for-your-health” substances that are currently so high profile?

O-ta

G-ko-san, you look a bit down.

G-ko

My vet says my blood sugar level is too high... That’s why I feel a little low.

O-ta

Maybe you can hear a story of hope to lift your spirits today.

Welcome, O-ta-kun and G-ko-chan! Do you know what “ketone bodies” are?

G-ko

Ketone bodies? I’ve never heard of them.

Tsubota

I see. Organisms usually use glucose as an energy source. So, what happens if glucose is not available in the body due to fasting or restricted hydrocarbon intake? In that case, body fat is broken down and converted into substances for consumption. These substances are ketone bodies.

O-ta & G-ko
O-ta

You mean ketone bodies are produced from fat?

Tsubota

That's right. Ketone bodies are naturally present in the body. Fat in the body is consumed as ketone bodies, and ketone bodies themselves are considered to be good for your health. So these substances are attracting growing attention, mainly in the U.S.

G-ko

How are they good for the health? You’ve really got my interest now!

Tsubota

That’s great. Two researchers will now explain them to you in detail.

A ground-breaking technology produced by Osaka Gas allows the manufacture of ketone bodies by a safe fermentation method!

Nishimura

There are high expectations of the great potential of ketone bodies, not only to aid dieting but also to prevent or control Alzheimer’s, diabetes, cancer and other diseases. Even ketone supplements exist.

G-ko

Ketone bodies are full of beneficial effects. I want a supplement right now! Where can I get them?

O-ta

Ok, G-ko-san, calm down. According to Mr. Tsubota, ketone bodies are made in the body, right? I guess the existence of supplements means ketone bodies can be artificially produced outside the body and taken...

Hannya

That’s right. For example, in the U.S., chemically synthesized ketone bodies are sold as supplements for athletes and dieters.

G-ko

What are such human-made ketone bodies made from?

Nishimura

Broadly speaking, ketone supplements currently available in the U.S. market are produced by chemical synthesis from a substance like petroleum.

O-ta

We take supplements into the body, so I guess supplements made from natural ingredients would be safer... Can’t we make ketone bodies from natural ingredients?

Hannya

O-ta-kun, that’s a very good question! Actually, Osaka Gas has developed a technology for mass-producing ketone bodies from natural ingredients!

Nishimura

We have even obtained a patent for its production process!

Here is the ketone body we produced!

O-ta & G-ko

The manufacturing technology was born through great “birth” pains!

G-ko

Why is Osaka Gas doing this? Osaka Gas doesn’t seem to have any connection with that field.

Tsubota

Before the technology was established, the Energy Technology Laboratories had researched a biogas technology for producing methane by fermenting waste water and garbage. However, since that research had limited applications, we were looking for new technologies and research themes.

G-ko

Fermentation was the key, right?

Tsubota

That’s right. We had also been engaged in developing fermentation-related technologies, including biopolymer-based trash bags that can be degraded by microbes. When conducting such research activities, we obtained information about the National Institute of Advanced Industrial Science and Technology (AIST)’s discovery that a bacterium called Halomonas has the function of generating a ketone body. Then, we launched joint research with AIST.

O-ta

Halomonas? I’ve never heard of it.

Halomonas looks like this. It looks like green soybeans...

Nishimura

I suppose not many people know about it, but it’s a bacterium that prefers environments with a high salt concentration. It’s often found in kimchi and seafood. We noticed that Halomonas would likely help us produce a ketone body through fermentation. We thought that there would be social needs for the ketone body made from natural ingredients through fermentation, rather than chemically synthesized ketone bodies. That’s why we began to develop a fermentative ketone body manufacturing technology as our biotechnological research theme.

O-ta

You tried to utilize Osaka Gas’s advanced fermentation technology.

Hannya

That’s right. We not only further improved our fermentation technology so that we could make full use of Halomonas. Actually, fermented ketone liquids generated by Halomonas contain various impurities... Therefore, we also really had to work hard through a lot of trial and error to separate and purify a ketone body, until we finally succeeded in producing a 99% ketone body!

Fermented ketone liquids are produced by putting Halomonas, sugar and other substances in this fermentation tank.

G-ko

Great! Your efforts produced a happy result.

Nishimura

No. Our goal is not to produce an almost pure ketone body. We need to mass-produce the substance to provide it to the market.

O-ta

Is there any big difference between making the ketone body in a test tube in the laboratory and mass-producing it?

Hannya

Yes, there’s a vast difference. There are a number of conditions necessary to produce the ketone body successfully, for example temperature. So, we began by creating an environment that met all the conditions in a small tank. Then, we had to make steady efforts to gradually enlarge the tank scale. In the laboratory, we could only produce a few grams of the ketone body at first. However, as our technological development progressed, we eventually succeeded in producing several tons of the substance in one production. It was really difficult to scale up the technology without changing the quality of the product.

G-ko

It’s hard for me to grasp the increase from several grams to several tons.

In short, it's like the difference between cooking curry at home and cooking it in a large pot in a school kitchen.

Hannya

The actual difference is greater... When you cook curry in a large pot, you have to prevent the ingredients from burning and sticking to the bottom of the pot, and from becoming thoroughly cooked through only near the inner surface of the pot, causing the vegetables to break up into little pieces. So, you should mix the ingredients well to produce a perfectly uniformly cooked curry. Mass production is a little like that.

G-ko

It sounds very hard.

Nishimura

But now you’ve got a clearer picture! In this way, we explored the optimal conditions for mass production in terms of the size of the tank, the temperature, the rate and frequency of stirring, the oxygen concentration, and so on. That required a long process of trial and error in the laboratory. The fermentation tank that we currently use is vertically high, so it isn’t easy to make the conditions of the fermented liquids uniform in the upper and lower parts of the tank. For example, the liquid in the upper part has a lower oxygen concentration, while the liquid in the lower part has a higher oxygen concentration under the pressure of the liquid in the upper part. It’s quite hard to understand the preferences of the bacteria clearly and meet the conditions necessary to have them work well.

O-ta

Such hard effort on your part has helped combine AIST’s technology with Osaka Gas’s original fermentation and separation technologies, resulting in your success in mass-producing the ketone body from natural ingredients.

Nishimura

That’s right!

Ketone bodies will contribute immensely to “healthy longevity”!

G-ko

But do we really need to make such large quantities of the ketone body? I can’t take so much of it.

Tsubota

You don't have to take it by yourself (laughs).

We firmly believe that ketone bodies have a wide variety of potential applications.

Tsubota

As explained before, ketone bodies are expected to help in dieting and prevent and control Alzheimer's, diabetes, cancer, and other diseases. In addition, the substances are also expected to have various other effects and applications, including antiaging, controlling myocardial infarction, improving motor functions, and preventing dementia.

Hannya

Moreover, the natural ingredient-based ketone body is produced only with Osaka Gas’s technology. Since ketone bodies have already come into vogue in the U.S., we will establish a system for stable mass-production in anticipation of growing demand for the substances in Japan, to enable us to meet the demand reliably.

O-ta

You said people in the U.S. take ketone body supplements. Will Osaka Gas produce and sell such supplements?

Nishimura

No. We are a raw material supplier. We hope to cooperate with various companies to provide ketone bodies in various forms to society. We will increase the appeal of the ketone body as a raw material, raise awareness of the substance among various companies, and collaborate with our partners in spreading Osaka Gas’s ketone body worldwide.

G-ko

I want you to make the substance easy for me to take.

O-ta

It may help improve your blood sugar level. I hope ketone bodies will spread quickly and allow people to live happier lives!

NishimuraHannyaTsubota, Hannya and Nishimura

That’s our professional aspiration!

That was a really good story. Thanks, guys! Thank you very much!

About the ketone body
The ketone body that Osaka Gas has succeeded in mass-producing with a bioprocess (fermentation) is (R)-3-hydroxybutyric acid (commonly known as 3HB or BHB).
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