Gentamicin sulfate prepared through enhanced microbial fermentation, and application method of gentamicin sulfate

Abstract

The invention claims to protect gentamicin sulfate prepared through enhanced microbial fermentation, and an application method of the gentamicin sulfate. The enhanced microbial engineering bacterium is a Micromonospora purpurea C2 1591 strain which is obtained by screening through a normal-pressure room-temperature plasma mutagenesis technology, and the Micromonospora purpurea C2 1591 strain is registered and collected in the China General Microbiological Culture Collection Center (CGMCC for short, the address is No.3, No.1 Yard, Beichen West Road, Chaoyang District, Beijing) on June 13, 2021, and the collection number is CGMCC No.59450. The screened engineering bacterium for directionally producing gentamicin C2 in high yield can directionally produce the gentamicin C2 in the high yield, the component ratio of gentamicin C2 is increased to 85% or above from the original about 15%, and the highest fermentation titer of an optimized formula is 1184 U / mL through Plackett-Burman design and is increased by 42% than the titer of an original formula. Compared with an original strain, the yield of the gentamicin C2 is increased by three times, in addition, other isomers or impurities are hardly contained, the gentamicin C2 can be directly applied downstream, complex biotransformation and purification is not required, a large amount of cost is saved, and an industrialization requirement is met.

Description

technical field

[0001] The invention belongs to the field of antibiotic pharmacy, and relates to an enhanced microbial fermentation to prepare gentamycin sulfate and its application method. Specifically, the invention relates to an engineering bacterium with a directional high-yield gentamicin C2 and its application. Antibiotic manufacturing. Background technique

[0002] Gentamicin was first discovered by Weinstein in 1963. It is a multi-component aminoglycoside antibiotic produced by Micromonospora, including C1, C2, C1a, C2a and C2b components. The main components of gentamicin, C1, C2 and C1a, are widely used clinically, among which C1a has the highest antibacterial activity, which is the precursor of etimicin synthesis, followed by C2b, also known as sagamycin . These antibiotics can bind to 16SrRNA on the 30S subunit of bacterial ribosomes, causing misreading of the genetic code, thereby blocking the synthesis of bacterial proteins, so they are mainly used to treat b...

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