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Fermentation production method of rifamycin SV based on oxygen uptake rate OUR used as control parameter

A technology of rifamycin and oxygen consumption rate, applied in the field of fermentation production of rifamycin SV, can solve problems such as no technical guidance scheme is given, and achieve the effects of improving fermentation production level, improving conversion rate and promoting synthesis

Active Publication Date: 2014-03-19
HEBEI XINGANG PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The above patent documents do not provide specific technical guidance on how the present invention can stably improve the fermentation production level and increase the yield of rifamycin SV

Method used

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  • Fermentation production method of rifamycin SV based on oxygen uptake rate OUR used as control parameter
  • Fermentation production method of rifamycin SV based on oxygen uptake rate OUR used as control parameter
  • Fermentation production method of rifamycin SV based on oxygen uptake rate OUR used as control parameter

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Embodiment 1

[0045] Embodiment 1: The fermentative production method of rifamycin SV of the present invention is to use Nocardia mediterranei as a starting strain, and generate rifamycin SV through purebred culture and three-stage fermentation. The specific process steps include the preparation of inclined planes process, mother bottle seed preparation process, first-level seed preparation process, second-level seed preparation process, and fermentation preparation process. Except for the fermentation preparation process, other processes are prior art. The further processing steps of each operation of the present invention are as follows:

[0046] (1) The preparation process of the slope: ①Preparation of the mother slope: according to the requirements of aseptic operation, pick an appropriate amount of sandy soil seeds with an inoculation needle, and evenly spread it on the slope medium. It is required to be uniform, sparse, and easy to select. Cultivate at a constant temperature for 9-10...

Embodiment 2

[0049] Embodiment 2: the fermentative production method of rifamycin SV of the present invention is to use Nocardia mediterranei as a starting strain, and generate rifamycin SV through purebred culture and three-stage fermentation, and the specific process steps include inclined plane Preparation process, mother bottle seed preparation process, primary seed preparation process, secondary seed preparation process, fermentation preparation process. In the fermentation preparation process, different oxygen supply levels are achieved by controlling the stirring speed and ventilation flow rate of the fermenter during the fermentation process, specifically within 74 to 75 hours in the early stage of the fermentation process (stirring speed is 550rpm, and the ventilation ratio of the fermenter is 1 : 0.8~0.9vvm) to maintain a high level of oxygen consumption rate OUR in the fermentation system is 20mmol / L / h (or 18 mmol / L / h), so that the titer rises rapidly, after 74~75 hours in the ea...

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Abstract

The invention discloses a fermentation production method of rifamycin SV based on oxygen uptake rate OUR used as a control parameter. By using nocardia intermedien as an original strain, rifamycin SV is produced by virtue of pure culture and three-level fermentation. In the fermentation preparation process, the stirring rotation speed of a fermentation tank and ventilation flow in the fermentation process are controlled to reach different oxygen supply levels; the oxygen uptake rate OUR of a fermentation system at high level is kept to be between 18 and 20mmol / L / h in 70-75 hours in the earlier stage of the fermentation process, so that hypha is quickly grown and the titer is quickly increased; after 70-75 hours in the earlier stage of the fermentation process, the stirring rotation speed of the fermentation tank and the ventilation flow are reduced, and the oxygen uptake rate OUR is controlled to be between 13 and 15mmol / L / h until the tank is put at the end. According to the method, the thallus growth and the synthesis of the rifamycin SV are increased, the conversion rate is increased, the production period is shortened, the fermentation production level is stably improved, and the yield of the rifamycin SV is improved.

Description

technical field [0001] The present invention relates to a fermentative production method of rifamycin SV, in particular to a fermentative production method of rifamycin SV based on the oxygen consumption rate OUR as a control parameter, especially the process in the fermentative production of rifamycin SV control related. Background technique [0002] Rifamycin antibiotics are a class of antibiotics produced by Streptococcus mediterranei. The role of Staphylococcus aureus is very strong. Also effective against some Gram-negative bacteria. Rifamycin drugs include: rifamycin B diethylamide, rifampicin and so on. Rifampicin, rifapentine and rifabutin are currently in clinical use. The immediate precursors of these drugs are all rifamycin SV. In the current rifamycin SV batch culture fermentation process, most of them only use pH, DO, temperature, etc. as the basis and means of control strategies. In most cases, these parameters can only reflect the performance or operatin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P17/18C12R1/01
Inventor 李海东刘爱军王泽建贾军巧张鑫庄英萍张嗣良张娅
Owner HEBEI XINGANG PHARMA
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