Substantial improvement of tetraene macrolide production in Streptomyces diastatochromogenes by cumulative drug resistance mutations

Abstract

Tetraene macrolides remain one of the most reliable fungicidal agents as resistance of fungal pathogens to these antibiotics is relatively rare. The modes of action and biosynthesis of polyene macrolides had been the focus of research over the past few years. However, few studies have been carried out on the overproduction of polyene macrolides. In the present study, cumulative drug-resistance mutation was used to obtain a quintuple mutant G5-59 with huge tetraene macrolide overproduction from the starting strain Streptomyces diastatochromogenes 1628. Through DNA sequence analysis, the mutation points in the genes of rsmG, rpsL and rpoB were identified. Additionally, the growth characteristic and expression level of tetrRI gene (belonging to the large ATP binding regulator of LuxR family) involved in the biosynthesis of tetraene macrolides were analyzed. As examined with 5L fermentor, the quintuple mutant G5-59 grew very well and the maximum productivity of tetramycin A, tetramycin P and tetrin B was as high as 1735, 2811 and 1500 mg/L, which was 8.7-, 16-and 25fold higher than that of the wild-type strain 1628, respectively. The quintuple mutant G5-59 could be useful for further improvement of tetraene macrolides production at industrial level.

Antimicrobials Affect the Fat Body Microbiome and Increase the Brown Planthopper Mortality

“…Toyocamycin is a nucleoside antibiotic and generated by the fermentation of Streptomyces diastatochromogenes 1,628. It exhibits both antibacterial and antifungal activities and effective against pathogenic fungi, including Rhizoctonia solani and Fusarium oxysporum ( Fan et al, 2020 ). Tebuconazole is a broad-spectrum triazole fungicide and causes DNA damage and induces the mitochondrial apoptotic pathway in the fungal pathogens of plants ( Muñoz-Leoz et al, 2011 ), which could affect the fungus in the fat body.…”

Physiology and Transcriptional Analysis of ppGpp-Related Regulatory Effects in Streptomyces diastatochromogenes 1628

“…5C ). Similarly, the transcriptional level of genes tetC and tetK ( 18 ) in tetraene macrolide cluster downregulated, while the expression of negatively transcriptional regulator tetR upregulated in the ppGpp 0 mutant by 2.29-fold at the late exponential phase, which was coherent with lower tetramycin P production ( Fig. 5D ).…”

“…Streptomyces produce various types of important bioactive metabolites, and many secondary metabolites were employed clinically as antibiotics. The two categories of secondary metabolites produced by S. diastatochromogenes 1628 have been identified as toyocamycin and tetramycin P, which was synthesized by the toy cluster (toyocamycin) ( 17 ) and the tetraene macrolide cluster (tetramycin P) ( 18 ). Previous studies showed that the stringent response could positively regulate the synthesis of secondary metabolism.…”

CdgB Regulates Morphological Differentiation and Toyocamycin Production in Streptomyces diastatochromogenes 1628

“…Streptomyces diastatochromogenes 1628 is an important Gram-positive bacterium that is used to produce several kinds of antibiotics, including toyocamycin, tetramycin A, tetramycin P, and tetrin B, which are widely used in the fields of medicine, agriculture, and food [1][2][3][4]. Among them, toyocamycin, an alkaline nucleoside antibiotic (Figure 1B), exhibits antibacterial and antifungal activities [5].…”