Transcriptional regulators of secondary metabolite biosynthesis in Streptomyces.

In the post-genome era, great progress has been made in metabolic engineering using recombinant DNA technology to enhance the production of high-value products by Streptomyces. With the development of microbial genome sequencing techniques and bioinformatic tools, a growing number of secondary metabolite (SM) biosynthetic gene clusters in Streptomyces and their biosynthetic logics have been uncovered and elucidated. In order to increase our knowledge about transcriptional regulators in SM of Streptomyces, this review firstly makes a comprehensive summary of the characterized factors involved in enhancing SM production and awakening SM biosynthesis. Future perspectives on transcriptional regulator engineering for new SM biosynthesis by Streptomyces are also provided.

Comparative Transcriptome Analysis of Two Chrysomycin-Producing Wild-Type and Mutant Strains of Streptomyces sp. 891.

Chrysomycin A (CA), a promising antibiotic agent, usually coexists with two analog chrysomycins B (CB) and C (CC) produced by several wild-type (WT) Streptomyces strains. With the aim to increase CA production, UV mutagenesis-based breeding had been employed on a marine-derived strain Streptomyces sp. 891 in our previous study and afforded an improved strain 891-B6 with enhanced CA yield. By comparative transcriptome analysis, significant differences in chrysomycin BGC-related gene expression between the WT strain 891 and the mutant strain 891-B6 were unveiled in the current study. Among 25 up-regulated genes in mutant 891-B6, chryA, chryB, chryC, chryF, chryG, chryK, chryP, and chryQ, responsible for the biosynthesis of benzonaphthopyranone aglycone, and chryD, chryE, and chryU in charge of production of its deoxyglycoside, were characterized. Furthermore, the expression of genes chryOII, chryOIII, and chryOIV responsible for the formation of 8-vinyl in CA from 8-ethyl in CB were greatly enhanced in strain 891-B6. These findings provide molecular mechanisms for increased yield of CA and decreased yield of CB for mutant 891-B6, which has potential application in industrial CA production.

Comprehensive Genomic Analysis of Marine Strain Streptomyces sp. 891, an Excellent Producer of Chrysomycin A with Therapeutic Potential.

Chrysomycin A is one of the most promising therapeutic candidates for treating infections caused by multidrug-resistant Gram-positive bacteria. By hybridizing next-step generation (Illumina) and third-generation (PacBio) sequencing technologies, a high-quality chromosome-level genome together with a plasmid was firstly assembled for chrysomycin A-producing marine strain 891. Phylogenetic analysis of the 16S rRNA gene and genome sequences revealed that this strain unambiguously belonged to the genus Streptomyces, and its genomic features and functional genes were comprehensively analyzed and annotated. AntiSMASH analysis of this strain unveiled one key biosynthetic gene cluster, T2PKS, responsible for the biosynthesis of chrysomycin, the biosynthesis pathway of which was putatively proposed. These findings definitely shed light on further investigation for construction of a robust industrial strain with high-yield chrysomycin A production using genetic engineering techniques and combinatorial biology approaches.