Genome-guided exploration of metabolic features of Streptomyces peucetius ATCC 27952: past, current, and prospect

Abstract

Streptomyces peucetius ATCC 27952 produces two major anthracyclines, doxorubicin (DXR) and daunorubicin (DNR), which are potent chemotherapeutic agents for the treatment of several cancers. In order to gain detailed insight on genetics and biochemistry of the strain, the complete genome was determined and analyzed. The result showed that its complete sequence contains 7187 protein coding genes in a total of 8,023,114 bp, whereas 87% of the genome contributed to the protein coding region. The genomic sequence included 18 rRNA, 66 tRNAs, and 3 non-coding RNAs. In silico studies predicted ~ 68 biosynthetic gene clusters (BCGs) encoding diverse classes of secondary metabolites, including non-ribosomal polyketide synthase (NRPS), polyketide synthase (PKS I, II, and III), terpenes, and others. Detailed analysis of the genome sequence revealed versatile biocatalytic enzymes such as cytochrome P450 (CYP), electron transfer systems (ETS) genes, methyltransferase (MT), glycosyltransferase (GT). In addition, numerous functional genes (transporter gene, SOD, etc.) and regulatory genes (afsR-sp, metK-sp, etc.) involved in the regulation of secondary metabolites were found. This minireview summarizes the genome-based genome mining (GM) of diverse BCGs and genome exploration (GE) of versatile biocatalytic enzymes, and other enzymes involved in maintenance and regulation of metabolism of S. peucetius. The detailed analysis of genome sequence provides critically important knowledge useful in the bioengineering of the strain or harboring catalytically efficient enzymes for biotechnological applications.

Insights into Streptomyces spp. isolated from the rhizospheric soil of Panax notoginseng: isolation, antimicrobial activity and biosynthetic potential for polyketides and non-ribosomal peptides

“…However, it is known that genome-sequencing projects on different actinobacteria have revealed a large number of biosynthetic gene clusters in each genome [44]. This viewpoint is proved by the genome information of Streptomyces peucetius ATCC 27952, possessing 68 biosynthetic gene clusters (BCGs) for various types of secondary metabolites, including non-ribosomal peptide synthase (NRPS), polyketide synthase (PKS I, II, and III), terpenes, and others [45]. Hence, the chosen primer system used in this work, in spite of favorable for the great majority of known PKS/NRPS genes, may not work in all cases of polyketides and nonribosomal peptides with uncommon molecular constructions.…”

Recent Advances in Strategies for Activation and Discovery/Characterization of Cryptic Biosynthetic Gene Clusters in Streptomyces

“…In addition, the availability of web-based tools, such as MASST [105], have enabled high-throughput screening of NPs based on their mass fragmentation patterns, which can enable the precise prediction of the metabolite from the culture broth, independent of the purification and structural elucidation steps. Furthermore, the available knowledge resources from genomics and metabolomics can be employed for strain engineering, biosynthetic pathway engineering, synthetic biology, systems biology, and media optimization technology for the production of such cryptic/known biomolecules in significant titers [106]. Such burgeoning development in both genetic studies, as well as metabolic profiling, can be further harnessed in metabolic engineering strategies by the application of computational approaches, such as artificial intelligence (AI).…”

Recent Advances in Exploration and Biotechnological Production of Bioactive Compounds in Three Cyanobacterial Genera: Nostoc, Lyngbya, and Microcystis

“…The genome of many cyanobacteria strains are already obtained, for e.g., N. punctiforme ATCC 29133 was sequenced which provided a better understanding about the distribution of secondary metabolites gene clusters (Moraes et al, 2017). Such availability of genome information can be combined with specific analytical tools to obtain the natural products and their biosynthetic pathways, which is most commonly defined as “genome mining” approach (Zerikly and Challis, 2009; Thuan et al, 2018). For example, the combination of mass spectrometric based metabolite profiling and genome analysis was established as a very powerful tool for obtaining columbamides, a new class of di- and trichlorinated acyl amides from cyanobacteria (Kleigrewe et al, 2015).…”