Microbial transformation preparation method for hydroxycamptothecin

Abstract

The invention belongs to the field of biotechnology, and particularly relates to a microbial transformation preparation method of hydroxycamptothecin. The invention conducts biotransformation to the camptotheca acuminata cells of a suspension culture by using non-toxic Aspergillus flavus Cr-1 strains (Aspergillus.flavus) and Rhizopus T-34 strains (Rhizopus sp.); the camptotheca acuminate cell cultures after the transformation experience separation and refining such as raw material crushing, reflex extraction, crystallization, silica gel column chromatography, crystallization, and the like, a pure hydroxycamptothecin product is obtained. The invention conducts biotransformation to the camptotheca acuminata cells of the suspension culture by using a microorganism so as to obtain a plant secondary metabolite hydroxycamptothecin which has an anti-tumor activity, wherein, the content of the plant secondary metabolite hydroxycamptothecin achieves 0.4% (g / g) of the dry weight of the cell; a new way of obtaining high-yield hydroxycamptothecin is established, thereby meeting the requirements of sustainable development; the method for separating the hydroxycamptothecin is simple, convenient and feasible; the purity of the product is high; therefore, the invention has good development prospect.

Description

technical field [0001] The invention belongs to the field of biotechnology. In particular, it relates to a preparation method for microbial conversion of hydroxycamptothecin. Background technique [0002] Since Wall et al. in the United States first extracted Campothecin (CPT) from Campotheca involucrata, a plant unique to China in 1966, the antitumor effect of this type of alkaloid has been widely concerned. In 1985, Hsiang expounded the mechanism of anti-tumor effect of this kind of drugs, and believed that camptothecin and its derivatives take DNA topoisomerase I as the target, and inhibit the synthesis of biological DNA to exert anti-tumor effect. This makes these drugs become the second hotspot in the research of plant-based anti-tumor drugs except paclitaxel. Among them, hydroxycamptothecin (Hydroxycamptoyhecin, HCPT) and topotecan (Topotecan, TPT) and irinotecan (Camptothecin-II, CPT-II) synthesized with hydroxycamptothecin as an intermediate have shown a wide range...

AI Technical Summary

Problems solved by technology

Hydroxycamptothecin is an alkaloid in the plant camptotheca. For a long time, Chinese enterprises have been directly extracting it from plants, but because of its low content and high production costs, it is difficult to meet clinical needs.

Subsequently, people have carried out a lot of research on the preparation of hydroxycamptothecin, including chemical total synthesis, chemical semi-synthesis, biotransformation and searching for new drug sources in related plants, etc., but for various reasons, these methods have not been used in industrialization. mass production

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