Method for activating expression of biosynthetic gene cluster of microbial recessive secondary metabolites

Abstract

The invention discloses a method for activating the expression of the biosynthetic gene cluster of microbial recessive secondary metabolites. The method utilizes the genetic engineering technology to partially or totally inactivate the biosynthetic gene cluster with microorganisms accounting for the major secondary metabolites so that the microorganisms do not produce or produce less corresponding secondary metabolites to obtain a relatively simple secondary metabolite background, and then by changing the culture conditions or genetic transformation, the yield of secondary metabolites that do not express or lowly express originally is significantly increased and the secondary metabolites become the main secondary metabolites, and are detected by the chemical or biological activity analysis and other methods until a number of new secondary metabolites. The method can significantly improve the success rate of recessive secondary metabolites biosynthesis gene cluster activation and product detection, and provide a new effective way for digging new active substances from a large number of microbial recessive secondary metabolites biosynthetic gene clusters.

Description

[0001] Technical field: [0002] The invention belongs to the technical fields of microbiology and genetic engineering, and in particular relates to a method for activating the expression of microbial recessive secondary metabolite biosynthetic gene clusters. [0003] Background technique: [0004] The emergence and spread of multidrug-resistant bacteria, the continuous emergence of new pathogenic bacteria and the lack of high-efficiency and low-toxicity anticancer drugs make the creation and development of new anti-infection and anti-cancer drugs a very necessary and urgent task. As important natural products, microbial secondary metabolites play an extremely important role in the process of modern drug discovery and development, and are an important way and source of drug innovation [Butler MS, et al., Natural Product Reports, 2014,31:1612 -1661]. However, after decades of excavation, high-frequency repeated discoveries have seriously affected the screening efficiency of act...

AI Technical Summary

Problems solved by technology

Methods such as polysin, interspecies crosstalk (co-culture) and ribosome engineering mainly rely on past experience and exquisite design, but it is difficult to predict the results and rational design in advance, which is inefficient; heterologous expression, For methods such as promoter modification, it is necessary to have a clear enough understanding of the genetic background and metabolic regulatory network of the producing bacteria, and the universality is low.

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