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[Drug Development From Natural Fermentation Products: Establishing a Manufacturing Process Which Maximizes the Potential of Microorganisms]

[Drug Development From Natural Fermentation Products: Establishing a Manufacturing Process Which Maximizes the Potential of Microorganisms]

Koji Nagao, Satoshi Ueda, Munekazu Kanda, Nobutaka Oohata, Michio Yamashita, Motohiro Hino

Yakugaku Zasshi. 2010 Nov;130(11):1471-8.

PMID: 21048405

Abstract:

Natural fermentation products have long been studied as attractive targets for drug discovery due to their amazing diverse, complex chemical structures and biological activities. As such, a number of revolutionary drugs developed from natural fermentation products have contributed to global human health. To commercialize a drug derived from natural fermentation products, an effective chemical entity must be identified and thoroughly researched, and an effective manufacturing process to prepare a commercial supply must be developed. To construct such a manufacturing process for tacrolimus and micafungin, the following studies were conducted: first, we focused on controlling the production of the tacrolimus-related compound FR900525, a fermentation by-product of tacrolimus which was critical for quality assurance of the drug substance. FR900525 production was reduced by using a mutant strain which produced more pipecolic acid, the biosynthesis material of tacrolimus, than the original strain. Then, to optimize the fermentation process of FR901379, an intermediate of micafungin, a fed-batch culture was adopted to increase FR901379 productivity. Additionally, FULLZONE(TM) impeller was installed into the scaled-up fermenter, reducing the agitation-induced damage to the mycelium. As a result, the mycelial form changed from filamentous to pellet-shaped, and the air uptake rate during fermentation was drastically improved. Finally, we conducted screening for FR901379 acylase-producing microorganisms, as FR901379 acylase is necessary to manufacture micafungin. We were able to easily discover FR901379 acylase-producing microorganisms in soil samples using our novel, convenient screening method, which involves comparing the difference in antibiotic activity between FR901379 and its deacylated product.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
CS31043269	Tacrolimus Related Compound A			Price

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