How scientists sequenced the complete genome of a remarkable bacterium from the Atacama Desert, revealing its potential for novel antibiotics and cancer treatments
Imagine a place so dry that some areas see rainfall only once every decade—the Atacama Desert in Chile, the driest non-polar desert on Earth. Yet within this seemingly barren landscape thrives an invisible universe of microbial life that has developed extraordinary survival strategies. Among these resilient inhabitants is Streptomyces leeuwenhoekii, a bacterial species that produces chemical compounds with remarkable potential to fight diseases, including novel antibiotics at a time when drug-resistant infections pose an increasing threat to global health 6 .
In 2015, a research team achieved a groundbreaking feat: they sequenced the complete genome of this fascinating bacterium, assembling its entire genetic blueprint into just three continuous pieces—a technical marvel that had previously been impossible 1 2 .
This scientific triumph didn't just reveal the genetic makeup of a desert survivor; it opened a treasure chest of potential new medicines and demonstrated how cutting-edge genetic technologies can help us mine nature's molecular diversity.
The Chaxa Lagoon in the Atacama Desert presents conditions that would be lethal to most life forms: intense ultraviolet radiation, dramatic temperature swings from below freezing to scorching heat, and water with extremely high salt content .
Even before the genome was sequenced, researchers knew S. leeuwenhoekii was special. Laboratory tests revealed it produces several biologically active compounds with potential medical applications 6 .
A group of antibiotics that show potent activity against dangerous bacteria like MRSA. Particularly exciting was the discovery that chaxamycin D also inhibits the ATPase activity of human Hsp90, a protein implicated in cancer, suggesting potential as an anti-cancer agent .
Large 22-membered macrolactone structures with potential therapeutic applications 1 .
A lasso peptide discovered from another strain of S. leeuwenhoekii (C58) found in the same desert environment 6 .
Actinobacteria, the group to which Streptomyces belongs, are renowned for their ability to produce specialized metabolites—complex chemical compounds that include the majority of antibiotics used in medicine today 1 . In fact, actinomycetes produce over 70% of the natural product scaffolds found in clinically used anti-infective agents 1 .
However, these bacteria have complex genomes that make them difficult to sequence. Their DNA has an unusually high GC content (approximately 72-73%, compared to about 50% in humans), which creates technical challenges for sequencing technologies 1 . Additionally, the genes for producing valuable compounds are often organized in biosynthetic gene clusters—groups of genes that work together to build complex molecules. These clusters frequently contain repetitive sequences that are difficult to assemble correctly with conventional sequencing methods 1 .
Could read up to 800-1000 base pairs at a time, accurate but slow and expensive for large genomes
Generates huge volumes of data quickly and cheaply, but reads are short (100-300 base pairs), making it hard to assemble repetitive regions
Produces much longer reads (thousands of base pairs), ideal for complex regions, but with slightly higher error rates
For S. leeuwenhoekii, the challenge was particularly pronounced because its biosynthetic gene clusters contained long repetitive sequences with nearly identical sections that short reads couldn't navigate properly—like trying to assemble a jigsaw puzzle where many pieces look almost the same 1 .
When researchers finally deciphered the complete genome of S. leeuwenhoekii, they discovered why this bacterium was so chemically talented: its DNA contained an astonishing 35 specialized metabolite gene clusters—groups of genes that work together to produce complex biological compounds 1 7 . This represented far more chemical potential than had been revealed through initial laboratory studies.
The genomic mining confirmed the presence of gene clusters for known compounds like chaxamycins and chaxalactins, but also revealed many previously unknown clusters, including:
| Cluster Type | Number Found | Known Examples | Potential Applications |
|---|---|---|---|
| Polyketide Synthase (PKS) | Multiple | Chaxamycins, Chaxalactins | Antibiotics, Anti-cancer drugs |
| Non-Ribosomal Peptide Synthetase (NRPS) | Multiple | Desferrioxamine E | Siderophore (iron chelation) |
| Lasso Peptides | 3 | Chaxapeptin | Various therapeutic applications |
| Hybrid PKS-NRPS | Multiple | Not characterized | Unknown novel compounds |
| Other | Multiple | Hygromycin A | Antibiotic |
This discovery highlighted the power of genome mining—using bioinformatic analysis to estimate the biosynthetic capacity of an organism before extensive laboratory work. As one research team noted, this approach "has already provided access to many novel biosynthetic pathways and metabolites that otherwise would have remained undetected" 1 .
To overcome the limitations of previous sequencing attempts, researchers devised a clever strategy that combined the strengths of two complementary technologies 1 :
This third-generation technology provided long reads—sometimes thousands of base pairs in length—that could span repetitive regions and help assemble large contiguous pieces of the genome.
This second-generation technology provided shorter reads but with higher accuracy, especially in difficult-to-sequence regions like homopolymeric runs of G and C bases.
The research team sequenced the same S. leeuwenhoekii DNA using both platforms and then integrated the results. The PacBio data provided the overall structure, assembling most of the chromosome and two plasmids into just three large contigs. The Illumina data then served as a proofreader, correcting errors that tended to occur in homopolymeric stretches in the PacBio sequence 1 .
This hybrid approach proved remarkably successful, generating what the researchers called "an almost complete chromosome sequence as well as the sequences of two plasmids as single contigs without recourse to gap-closing or sequencing of clones from a genomic library; to our knowledge, this is the first time that this has been achieved with an actinomycete" 1 .
The completed genome assembly revealed three distinct replicons:
The hybrid sequencing approach proved essential for accuracy. When researchers compared the PacBio and Illumina assemblies, they found that the PacBio sequence had frequent single-base omissions in runs of identical G or C bases. By using the Illumina data for correction, they inserted 2,934 missing bases and made an additional 42 base changes—totaling 2,976 corrections in the final 7.9 million base chromosome (an error rate of just 0.038%) 1 .
| Replicon | Type | Size | GC Content | Assembly Result |
|---|---|---|---|---|
| Chromosome | Linear | ~7.9 Mb | ~72% | Single contig |
| pSLE1 | Circular | ~86 kb | Not specified | Single contig |
| pSLE2 | Linear | ~132 kb | Not specified | Single contig |
| Previous Illumina-only assembly | - | ~7.86 Mb | ~72% | 658 contigs |
Behind every successful genome sequencing project lies an array of specialized reagents and tools. Here are some of the essential components that made the S. leeuwenhoekii genome sequencing possible:
| Tool/Reagent | Function | Role in This Study |
|---|---|---|
| PacBio SMRT Cells | Generate long sequence reads | Span repetitive regions in biosynthetic gene clusters |
| Illumina MiSeq Reagents | Produce high-accuracy short reads | Correct errors in homopolymeric regions |
| High GC Content DNA Extraction Kits | Isolate quality DNA from actinomycetes | Obtain sufficient high-molecular-weight DNA from S. leeuwenhoekii |
| Genome Assembly Software | Computational sequence assembly | Convert raw reads into contiguous sequences |
| Artemis Visualization Tool | Genome browser and annotation tool | Identify coding sequences and analyze GC-frame plots |
The successful sequencing of Streptomyces leeuwenhoekii represents more than just technical achievement—it heralds a new approach to natural product discovery. By combining third-generation sequencing technologies with traditional chemistry, scientists can now rapidly assess the biochemical potential of microorganisms, including those that may be difficult to grow in laboratory conditions 1 .
This work has demonstrated that extreme environments like the Atacama Desert harbor microorganisms with unique genetic adaptations and biosynthetic capabilities .
As the threat of antibiotic-resistant infections continues to grow, such genome-guided explorations of nature's chemical diversity become increasingly valuable in the search for new therapeutic agents.
The legacy of this research extends beyond the specific compounds discovered in S. leeuwenhoekii. The experimental pipeline developed—using Illumina assembled contigs to complement PacBio sequencing—provides a roadmap for future studies seeking to unlock genetic secrets from other challenging organisms 1 . As we continue to explore the microbial world, such integrated approaches will undoubtedly reveal new chemical treasures with potential to address pressing human health challenges.
The sequencing of gifted microorganisms like S. leeuwenhoekii reminds us that even in Earth's most inhospitable places, nature has been busy devising sophisticated chemistry that we're only beginning to understand and appreciate.