Genome sequencing has revealed that actinomycetes possess the potential to produce many more secondary metabolites than previously thought. The existing challenge is to devise efficient methods to activate these silent biosynthetic gene clusters (BGCs). In Streptomyces ansochromogenes, disruption of wblA, a pleiotropic regulatory gene, activated the expression of cryptic tylosin analogues and abolished nikkomycin production simultaneously.
View Article and Find Full Text PDFAntibiotics (Basel)
September 2021
With the increase of drug resistance caused by the improper use and abuse of antibiotics, human beings are facing a global health crisis. Sequencing of genomes revealed the presence of an important reservoir of secondary metabolic gene clusters for previously unsuspected products with potentially valuable bioactivity. It has therefore become necessary to activate these cryptic pathways through various strategies.
View Article and Find Full Text PDFMureidomycins (MRDs), a group of unique uridyl-peptide antibiotics, exhibit antibacterial activity against the highly refractory pathogen Pseudomonas aeruginosa. Our previous study showed that the cryptic MRD biosynthetic gene cluster (BGC) mrd in Streptomyces roseosporus NRRL 15998 could not be activated by its endogenous regulator 02995 but activated by an exogenous activator SsaA from sansanmycin's BGC ssa of Streptomyces sp. strain SS.
View Article and Find Full Text PDFChlorothricin (CHL), produced by DSM 40725 (wild-type strain, WT), belongs to a growing family of spirotetronate antibiotics that have biological activities inhibiting pyruvate carboxylase and malate dehydrogenase. ChlF2, a cluster-situated SARP regulator, can activate the transcription of , , , , , and to control CHL biosynthesis. Co-expression of and encoding type II thioesterase in WT strain under the control of P led to high production of chlorothricin by 840% in comparison with that of WT.
View Article and Find Full Text PDFNeomycin, a multicomponent aminoglycoside antibiotic, is mainly utilized in livestock husbandry and feed additives in animals. The antimicrobial potency of the main product neomycin B is higher than that of its stereoisomer neomycin C. However, the content of neomycin C as an impurity in the high-producing strain is relatively high, and its isolation or removal from neomycin B is quite difficult, which influences the widespread application of neomycin.
View Article and Find Full Text PDFStaurosporine, belonging to indolocarbazole compounds, is regarded as an excellent lead compound for synthesizing antitumor agents as a potent inhibitor against various protein kinases. In this study, two separate clusters (cluster A and cluster B), corresponding to biosyntheses of K-252c (staurosporine aglycone) and sugar moiety, were identified in Streptomyces fradiae CGMCC 4.576 and heterologously expressed in Streptomyces coelicolor M1146 separately or together.
View Article and Find Full Text PDFNeomycin, an aminoglycoside antibiotic, is widely used in the livestock husbandry due to its higher antimicrobial activity and availability of feed additives in animals. However, its production yield is relatively low and cannot meet the needs of developing market and clinical application. Here, the entire natural neo cluster was cloned from Streptomyces fradiae CGMCC 4.
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