Insights into naturally minimised Streptomyces albus J1074 genome

Abstract

Background: The Streptomyces albus J1074 strain is one of the most widely used chassis for the heterologous production of bioactive natural products. The fast growth and an efficient genetic system make this strain an attractive model for expressing cryptic biosynthetic pathways to aid drug discovery.

Results: To improve its capabilities for the heterologous expression of biosynthetic gene clusters, the complete genomic sequence of S. albus J1074 was obtained. With a size of 6,841,649 bp, coding for 5,832 genes, its genome is the smallest within the genus streptomycetes. Genome analysis revealed a strong tendency to reduce the number of genetic duplicates. The whole transcriptomes were sequenced at different time points to identify the early metabolic switch from the exponential to the stationary phase in S. albus J1074.

Conclusions: S. albus J1074 carries the smallest genome among the completely sequenced species of the genus Streptomyces. The detailed genome and transcriptome analysis discloses its capability to serve as a premium host for the heterologous production of natural products. Moreover, the genome revealed 22 additional putative secondary metabolite gene clusters that reinforce the strain's potential for natural product synthesis.

Figure 1

Genomic sequence comparison of three Streptomyces strains. (A)S. albus versus S. coelicolor; (B)S. albus versus S. bingchenggensis were generated with NUCmer using default settings. Matches on the same strand are in red, and those on the opposite strand are in blue. The black bar at the bottom denotes the core region, which for S. albus contains almost the entire chromosome.

Figure 2

Features of linear S. albus J1074 chromosome. (A) GC-skew pattern of S. albus J1074 chromosome showing overrepresentation of C over G (yellow) and G over C (blue) in the strand analysed; (B) Distribution of mobile elements though the S. albus chromosome. The origin of replication is marked with a blue triangle.

Figure 3

BLASTCLUST classification of proteins into clusters. A total of 5851 S. albus, 7768 S. coelicolor, and 10022 S. bingchenggensis proteins were classified. The number of shared and unique clusters, not proteins, is shown.

Figure 4

Biosynthetic gene clusters identified in the genome of S. albus J1074.

Figure 5

Transcription levels of ribosomal proteins. Transcription levels measured in FPKM of genes coding for the genes encoding ribosomal proteins S8 (XNR_3743), L6 (XNR_3744), L18 (XNR_3745), S5 (XNR_3746), L30 (XNR_3747) and L15 (XNR_3748) at 12, 36 and 60 h after culture inoculation.

Figure 6

Transcription levels of PhoPR regulatory system. Transcription levels measured in FPKM of XNR_5270 (phoP) and XNR_5271 (phoR) genes at 12, 36 and 60 h after culture inoculation.