Endophytic Strain Selection for Stable High-Yield Camptothecin

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Solution Overview

Problem

The existing methods for obtaining camptothecin from medicinal plants like Camptotheca acuminata are inefficient due to low content and difficult extraction, while endophytic fungi exhibit poor genetic stability limiting industrial application.

Innovation Solution

Isolation and identification of high-yield endophytic bacterial strains, specifically Alternaria tenuissima ZCMUKL-S1, Alternaria citricancri ZCMUKL-S2, and Aspergillus versicolor ZCMUKL-S3, which are deposited with CCTCC numbers, and their cultivation in a potato glucose agar medium under specific conditions to produce camptothecin.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If camptothecin is extracted directly from Camptotheca acuminata, then the source is available, but the content is low and extraction is very difficult

Engineering Contradiction:
Improvecamptothecin contentVSAvoidextraction difficulty
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent uses endophytic bacteria as an intermediary organism to produce camptothecin. Instead of directly extracting from the plant, the endophytic bacteria isolated from Camptotheca acuminata serve as a mediator that synthesizes camptothecin through fermentation, thereby avoiding the difficulties of direct plant extraction while achieving high yields.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If endophytic fungi are used for camptothecin production, then culture cost is low and growth is rapid, but genetic stability is poor

Engineering Contradiction:
Improvecamptothecin yieldVSAvoidgenetic stability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent employs endophytic bacteria that can copy or replicate the camptothecin production capability with high genetic stability. The bacterial strains isolated and screened in this patent demonstrate stable inheritance of camptothecin synthesis genes, allowing for reliable industrial fermentation without the genetic instability problems associated with endophytic fungi.

Inventive Principle:
Principle #26Copying

3Ease of manufacture

If endophytic fungi are used for camptothecin production, then culture cost is low and growth is rapid, but industrial application is limited

Engineering Contradiction:
Improveculture costVSAvoidindustrial applicability
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent utilizes endophytic bacteria that can be easily cultured in inexpensive media and complete their fermentation cycle rapidly. The bacteria can be disposed of after a single fermentation cycle, and new cultures can be prepared quickly due to their rapid growth characteristics, making them economically viable for industrial production.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Productivity

If conventional extraction methods are used, then the process is simple, but the yield is insufficient to meet market demand

Engineering Contradiction:
Improvecamptothecin yieldVSAvoidproduction process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent changes the fundamental parameter of production from plant extraction to microbial fermentation. By utilizing endophytic bacteria that naturally produce camptothecin, the system achieves high yields through controlled fermentation processes, transforming a low-yield extraction process into a high-yield bioproduction process while maintaining operational simplicity.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS12509710B2Endophytic bacterial strain for preparing camptothecin and preparation method of camptothecin
Publication Date: 2025.12.30 ZHEJIANG CHINESE MEDICAL UNIVERSITY
  • US12509710B2 patent drawing
  • US12509710B2 patent drawing
  • US12509710B2 patent drawing

AI summary

The present application provides an endophytic bacterial strain with a high camptothecin yield, which is Alternaria temuissima ZCMUKL-S1, deposited as CCTCC NO: M2021189, or Alternaria citricancri ZCMUKL-S2, deposited as CCTCC NO: M2021190, or Aspergillus versicolor ZCMUKL-S3, deposited as CCTCC NO: M2021191. The endophytic bacterial strain has a high yield of camptothecin, wherein the yield of camptothecin per unit dry mycelium powder of Aspergillus versicolor ZCMUKL-S3 is as high as 116 μg/g, which is the highest yield of camptothecin produced by endophytic bacterial strains reported at present, and has potential application value for its industrial production. In addition, the endophytic bacterial strain which can produce high camptothecin provided by the present application has good genetic stability.