Tapping Into Actinobacterial Genomes for Natural Product Discovery

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2021 Jul 9

PMID 34239507

Citations 12

Authors

Tanim Arpit Singh

Ajit Kumar Passari

Anjana Jajoo

Sheetal Bhasin

Vijai Kumar Gupta

Abeer Hashem

Abdulaziz A Alqarawi

Elsayed Fathi Abd Allah

Affiliations

Soon will be listed here.

Abstract

The presence of secondary metabolite biosynthetic gene clusters (BGCs) makes actinobacteria well-known producers of diverse metabolites. These ubiquitous microbes are extensively exploited for their ability to synthesize diverse secondary metabolites. The extent of their ability to synthesize various molecules is yet to be evaluated. Current advancements in genome sequencing, metabolomics, and bioinformatics have provided a plethora of information about the mechanism of synthesis of these bioactive molecules. Accessing the biosynthetic gene cluster responsible for the production of metabolites has always been a challenging assignment. The genomic approach developments have opened a new gateway for examining and manipulating novel antibiotic gene clusters. These advancements have now developed a better understanding of actinobacterial physiology and their genetic regulation for the prolific production of natural products. These new approaches provide a unique opportunity to discover novel bioactive compounds that might replenish antibiotics' exhausted stock and counter the microbes' resistance crisis.

Citing Articles

Amphibian skin bacteria contain a wide repertoire of genes linked to their antifungal capacities.

Gonzalez-Serrano F, Romero-Contreras Y, Orta A, Basanta M, Morales H, Sandoval Garcia G World J Microbiol Biotechnol. 2025; 41(3):78.

PMID: 40011297 PMC: 11865118. DOI: 10.1007/s11274-025-04292-z.

Genomic and Phenotypic Characterization of sp. nov., Amicetin-Producing Actinobacteria Isolated from Bamboo Rhizospheric Soil.

Zakalyukina Y, Alferova V, Nikandrova A, Kiriy A, Chernyshova A, Kabilov M Microorganisms. 2025; 12(12.

PMID: 39770830 PMC: 11677201. DOI: 10.3390/microorganisms12122628.

Biosynthetic gene clusters with biotechnological applications in novel Antarctic isolates from Actinomycetota.

Bruna P, Nunez-Montero K, Contreras M, Leal K, Garcia M, Abanto M Appl Microbiol Biotechnol. 2024; 108(1):325.

PMID: 38717668 PMC: 11078813. DOI: 10.1007/s00253-024-13154-x.

Mining the microbiome of Lake Afdera to gain insights into microbial diversity and biosynthetic potential.

Balcha E, Macey M, Gemeda M, Cavalazzi B, Woldesemayat A FEMS Microbes. 2024; 5:xtae008.

PMID: 38560625 PMC: 10979467. DOI: 10.1093/femsmc/xtae008.

Manipulation and epigenetic control of silent biosynthetic pathways in actinobacteria.

Karimian S, Farahmandzad N, Mohammadipanah F World J Microbiol Biotechnol. 2024; 40(2):65.

PMID: 38191749 DOI: 10.1007/s11274-023-03861-4.

References

Asolkar R, Kirkland T, Jensen P, Fenical W . Arenimycin, an antibiotic effective against rifampin- and methicillin-resistant Staphylococcus aureus from the marine actinomycete Salinispora arenicola. J Antibiot (Tokyo). 2009; 63(1):37-9. PMC: 2825372. DOI: 10.1038/ja.2009.114. View

Fiedler H, Bruntner C, Riedlinger J, Bull A, Knutsen G, Goodfellow M . Proximicin A, B and C, novel aminofuran antibiotic and anticancer compounds isolated from marine strains of the actinomycete Verrucosispora. J Antibiot (Tokyo). 2008; 61(3):158-63. DOI: 10.1038/ja.2008.125. View

Nithya K, Muthukumar C, Biswas B, Alharbi N, Kadaikunnan S, Khaled J . Desert actinobacteria as a source of bioactive compounds production with a special emphases on Pyridine-2,5-diacetamide a new pyridine alkaloid produced by Streptomyces sp. DA3-7. Microbiol Res. 2018; 207:116-133. DOI: 10.1016/j.micres.2017.11.012. View

Gomez-Escribano J, Bibb M . Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters. Microb Biotechnol. 2011; 4(2):207-15. PMC: 3818861. DOI: 10.1111/j.1751-7915.2010.00219.x. View

Eustaquio A, Gust B, Galm U, Li S, Chater K, Heide L . Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters. Appl Environ Microbiol. 2005; 71(5):2452-9. PMC: 1087579. DOI: 10.1128/AEM.71.5.2452-2459.2005. View

Hwee Lim Y, Wong F, Yeo W, Ching K, Lim Y, Heng E . Auroramycin: A Potent Antibiotic from Streptomyces roseosporus by CRISPR-Cas9 Activation. Chembiochem. 2018; . DOI: 10.1002/cbic.201800266. View

Chen Y, Liu X, Lv F, Li P . Characterization of three regulatory genes involved in enduracidin biosynthesis and improvement of enduracidin production in Streptomyces fungicidicus. J Appl Microbiol. 2019; 127(6):1698-1705. DOI: 10.1111/jam.14417. View

Genilloud O, Gonzalez I, Salazar O, Martin J, Tormo J, Vicente F . Current approaches to exploit actinomycetes as a source of novel natural products. J Ind Microbiol Biotechnol. 2010; 38(3):375-89. DOI: 10.1007/s10295-010-0882-7. View

Axenov-Gribanov D, Axenov-Gibanov D, Voytsekhovskaya I, Tokovenko B, Protasov E, Gamaiunov S . Actinobacteria Isolated from an Underground Lake and Moonmilk Speleothem from the Biggest Conglomeratic Karstic Cave in Siberia as Sources of Novel Biologically Active Compounds. PLoS One. 2016; 11(2):e0149216. PMC: 4764329. DOI: 10.1371/journal.pone.0149216. View

10.

Genilloud O . Mining Actinomycetes for Novel Antibiotics in the Omics Era: Are We Ready to Exploit This New Paradigm?. Antibiotics (Basel). 2018; 7(4). PMC: 6316141. DOI: 10.3390/antibiotics7040085. View

11.

Silva L, Crevelin E, Souza D, Lacerda-Junior G, Oliveira V, Ruiz A . Actinobacteria from Antarctica as a source for anticancer discovery. Sci Rep. 2020; 10(1):13870. PMC: 7431910. DOI: 10.1038/s41598-020-69786-2. View

12.

Zhou M, Jing X, Xie P, Chen W, Wang T, Xia H . Sequential deletion of all the polyketide synthase and nonribosomal peptide synthetase biosynthetic gene clusters and a 900-kb subtelomeric sequence of the linear chromosome of Streptomyces coelicolor. FEMS Microbiol Lett. 2012; 333(2):169-79. DOI: 10.1111/j.1574-6968.2012.02609.x. View

13.

Sugiura T, Ariyoshi Y, Negoro S, Nakamura S, Ikegami H, Takada M . Phase I/II study of amrubicin, a novel 9-aminoanthracycline, in patients with advanced non-small-cell lung cancer. Invest New Drugs. 2005; 23(4):331-7. DOI: 10.1007/s10637-005-1441-3. View

14.

Rodriguez Estevez M, Gummerlich N, Myronovskyi M, Zapp J, Luzhetskyy A . Benzanthric Acid, a Novel Metabolite From Del14 Expressing the Nybomycin Gene Cluster. Front Chem. 2020; 7:896. PMC: 6965495. DOI: 10.3389/fchem.2019.00896. View

15.

Li L, Wei K, Zheng G, Liu X, Chen S, Jiang W . CRISPR-Cpf1-Assisted Multiplex Genome Editing and Transcriptional Repression in Streptomyces. Appl Environ Microbiol. 2018; 84(18). PMC: 6121969. DOI: 10.1128/AEM.00827-18. View

16.

Doroghazi J, Albright J, Goering A, Ju K, Haines R, Tchalukov K . A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nat Chem Biol. 2014; 10(11):963-8. PMC: 4201863. DOI: 10.1038/nchembio.1659. View

17.

Baral B, Akhgari A, Metsa-Ketela M . Activation of microbial secondary metabolic pathways: Avenues and challenges. Synth Syst Biotechnol. 2018; 3(3):163-178. PMC: 6190515. DOI: 10.1016/j.synbio.2018.09.001. View

18.

Tong Y, Charusanti P, Zhang L, Weber T, Lee S . CRISPR-Cas9 Based Engineering of Actinomycetal Genomes. ACS Synth Biol. 2015; 4(9):1020-9. DOI: 10.1021/acssynbio.5b00038. View

19.

Zhang M, Wong F, Wang Y, Luo S, Hwee Lim Y, Heng E . CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters. Nat Chem Biol. 2017; . PMC: 5634907. DOI: 10.1038/nchembio.2341. View

20.

Qian Z, Bruhn T, DAgostino P, Herrmann A, Haslbeck M, Antal N . Discovery of the Streptoketides by Direct Cloning and Rapid Heterologous Expression of a Cryptic PKS II Gene Cluster from sp. Tü 6314. J Org Chem. 2019; 85(2):664-673. DOI: 10.1021/acs.joc.9b02741. View