An intricate regulation of WblA controlling production of silent tylosin analogues and abolishment of expressible nikkomycin.

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.

Activation of Cryptic Antibiotic Biosynthetic Gene Clusters Guided by RNA-seq Data from Both and ΔwblA.

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.

Molecular mechanism of mureidomycin biosynthesis activated by introduction of an exogenous regulatory gene ssaA into Streptomyces roseosporus.

Mureidomycins (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.

Co-expression of a SARP Family Activator ChlF2 and a Type II Thioesterase ChlK Led to High Production of Chlorothricin in DSM 40725.

Chlorothricin (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.

Component Optimization of Neomycin Biosynthesis via the Reconstitution of a Combinatorial Mini-Gene-Cluster in .

Neomycin, 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.

Important role of a LAL regulator StaR in the staurosporine biosynthesis and high-production of Streptomyces fradiae CGMCC 4.576.

Staurosporine, 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.

Enhancement of neomycin production by engineering the entire biosynthetic gene cluster and feeding key precursors in Streptomyces fradiae CGMCC 4.576.

Neomycin, 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.