A 6.0 kb DNA fragment related to nikkomycin biosynthesis was cloned from nikkomycin-producing Streptomyces ansochromogenes 7100. Sequence analysis showed that the 1.9 kb Tth111 I fragment, a part of the 6.0 kb DNA fra...A 6.0 kb DNA fragment related to nikkomycin biosynthesis was cloned from nikkomycin-producing Streptomyces ansochromogenes 7100. Sequence analysis showed that the 1.9 kb Tth111 I fragment, a part of the 6.0 kb DNA fragment, contains one complete ORF designated sanB (GenBank accession No. AF224501), which is composed of 1740 bp encoding a protein consisting of 580 amino acid residues. Its start codon is GTG at 100 bp position and stop codon is TGA at 1840-bp position. Database searching indicated that the deduced protein of sanB is homologous to the histidinol-phosphate aminotransferase in Streptomyces coelicolor with 31% identities and 47% positives. Gene disruption was performed to study the function of sanB. It was found that disruptants of sanB lost the ability to synthesize nikkomycin, which reveals that sanB is a novel gene essential for nikkomycin biosynthesis.展开更多
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...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 wbl A,a pleiotropic regulatory gene,activated the expression of cryptic tylosin analogues and abolished nikkomycin production simultaneously.Overexpressing pathway-specific regulatory genes tylR1 and tylR2 can also trigger the biosynthesis of silent tylosin analogues,in which TylR1 exerted its function via enhancing tylR2 expression.Bacterial one-hybrid system experiments unveiled that Wbl A directly inhibits the transcription of tylR1 and tylR2 to result in the silence of tylosin analogues BGC.Furthermore,Wbl A can activate the nikkomycin production through up-regulating the transcription of pleiotropic regulatory gene adp A.More interestingly,Adp A can activate san G(an activator gene in nikkomycin BGC)but repress wbl A.Our studies provide a valuable insight into the complex functions of pleiotropic regulators.展开更多
文摘A 6.0 kb DNA fragment related to nikkomycin biosynthesis was cloned from nikkomycin-producing Streptomyces ansochromogenes 7100. Sequence analysis showed that the 1.9 kb Tth111 I fragment, a part of the 6.0 kb DNA fragment, contains one complete ORF designated sanB (GenBank accession No. AF224501), which is composed of 1740 bp encoding a protein consisting of 580 amino acid residues. Its start codon is GTG at 100 bp position and stop codon is TGA at 1840-bp position. Database searching indicated that the deduced protein of sanB is homologous to the histidinol-phosphate aminotransferase in Streptomyces coelicolor with 31% identities and 47% positives. Gene disruption was performed to study the function of sanB. It was found that disruptants of sanB lost the ability to synthesize nikkomycin, which reveals that sanB is a novel gene essential for nikkomycin biosynthesis.
基金supported by the National Key Research and Development Program of China(2020YFA0907800)the National Natural Science Foundation of China(32170043,82173720)the Beijing Natural Science Foundation(7212153)。
文摘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 wbl A,a pleiotropic regulatory gene,activated the expression of cryptic tylosin analogues and abolished nikkomycin production simultaneously.Overexpressing pathway-specific regulatory genes tylR1 and tylR2 can also trigger the biosynthesis of silent tylosin analogues,in which TylR1 exerted its function via enhancing tylR2 expression.Bacterial one-hybrid system experiments unveiled that Wbl A directly inhibits the transcription of tylR1 and tylR2 to result in the silence of tylosin analogues BGC.Furthermore,Wbl A can activate the nikkomycin production through up-regulating the transcription of pleiotropic regulatory gene adp A.More interestingly,Adp A can activate san G(an activator gene in nikkomycin BGC)but repress wbl A.Our studies provide a valuable insight into the complex functions of pleiotropic regulators.
