Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Apr 22;10(5):483.
doi: 10.3390/antibiotics10050483.

Actinomycetes: A Never-Ending Source of Bioactive Compounds-An Overview on Antibiotics Production

Davide De Simeis  1 , Stefano Serra  1
Affiliations
Review

Actinomycetes: A Never-Ending Source of Bioactive Compounds-An Overview on Antibiotics Production

Davide De Simeis et al. Antibiotics (Basel). .

Abstract

The discovery of penicillin by Sir Alexander Fleming in 1928 provided us with access to a new class of compounds useful at fighting bacterial infections: antibiotics. Ever since, a number of studies were carried out to find new molecules with the same activity. Microorganisms belonging to Actinobacteria phylum, the Actinomycetes, were the most important sources of antibiotics. Bioactive compounds isolated from this order were also an important inspiration reservoir for pharmaceutical chemists who realized the synthesis of new molecules with antibiotic activity. According to the World Health Organization (WHO), antibiotic resistance is currently one of the biggest threats to global health, food security, and development. The world urgently needs to adopt measures to reduce this risk by finding new antibiotics and changing the way they are used. In this review, we describe the primary role of Actinomycetes in the history of antibiotics. Antibiotics produced by these microorganisms, their bioactivities, and how their chemical structures have inspired generations of scientists working in the synthesis of new drugs are described thoroughly.

Keywords: Actinomycetes; antibiotic resistance; antibiotics; chemical synthesis; chemical tailoring; natural products.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic view of an operon: promoter (P); operator (O); operon gene and terminator (T).
Figure 2
Figure 2
Schematic representation of a eukaryotic and prokaryotic ribosome.
Figure 3
Figure 3
Peptidoglycan cross-linking mediated by DD-transpeptidase. The “serpentine” attached to NAM in black represents the peptide chain. The enzyme image is kindly taken by PDB [36].
Figure 4
Figure 4
Base structural nucleus of β-lactam antibiotics and some representative examples of natural beta-lactam antibiotics produced by Actinomycetes [38,39,40,41,42,43,44,45,46,47,48,49,50,51].
Figure 5
Figure 5
Natural and synthetic ansamycins: rifamycin B (natural) and rifampicin (semisynthetic).
Figure 6
Figure 6
Macrolide molecules produce by Actinomycetes: erythromycin A (antibiotic), and rapamycin (immunosuppressant).
Figure 7
Figure 7
Natural and synthetic lincosamides: lincomycin (natural) and clindamycin (semisynthetic).
Figure 8
Figure 8
Natural tetracycline: chlortetracycline (13), oxytetracycline (14), tetracycline (15), and 6-demethyltetracycline (16).
Figure 9
Figure 9
Selected examples of natural aminoglycosides: streptomycin, neomycin, paromomycin, tobramycin, kanamycin and gentamycin [38,39,53,85,86,87,88,89,90,91].
Figure 10
Figure 10
Schematic representation of an NRPS enzyme. A gene codifies for a module; each module is specific for the sequence and for the final structure of the peptidic product; each module possess catalytic domains: the main are the activation domain (green, A), carrier protein (yellow, PCP), condensation domain (red, C), modification domain (black, E), and termination domain (light blue, TE).
Figure 11
Figure 11
Selected examples of natural peptide antibiotics produced by Actinomycetes: vancomycin, daptomycin, pristinamycin II (streptogramin A type), and pristinamycin I (streptogramin B type) [38,39,105,106,107,108,109].
Figure 12
Figure 12
The natural aminocoumarin novobiocin and the epoxide antibiotic fosfomycin.
Figure 13
Figure 13
Milestone compounds in penicillin production: penicillin G, penicillin V, and 6-aminopenicillanic acid (6-APA).
Figure 14
Figure 14
The industrial processes to 6-aminopenicillanic acid (6-APA).
Figure 15
Figure 15
The transformation of penicillin sulfoxides through Morin rearrangement (upper pathway) or through Kukolja rearrangement.
Figure 16
Figure 16
The industrial synthesis of 7-aminodeacetoxycephalosporanic acid (7-ADCA).
Figure 17
Figure 17
The key synthetic steps of the synthesis of cefaclor® by Eli Lilly Company. PG = protecting group. Reagents and conditions: (a) NCS, toluene, reflux; (b) SnCl4, CH2Cl2, rt; (c) O3, CH2Cl2, −70 °C; (d) (PhO)3PCl2, CH2Cl2, −15 °C then iBuOH; (e) 2-amino-2-phenylacetylchloride; deprotection.
Figure 18
Figure 18
The chemical sensitivity of natural tetracyclines exemplified with aureomycin and terramycin degradation in basic and acidic environments, respectively. Tetracycline numbering is reported for aureomycin.
Figure 19
Figure 19
The synthetic approaches to the most relevant semisynthetic tetracyclines.
Figure 20
Figure 20
The key steps of the Myers approach to fully synthetic tetracyclines.
Figure 21
Figure 21
Eravacycline synthesis according to the Myers process.
Figure 22
Figure 22
The chemical structures of lipiarmycins.
Figure 23
Figure 23
The chemical degradation of lipiarmycin A3 and tiacumicin B allows assigning (18S,19R) absolute configuration. Reagents and conditions: (a) KOH aq.; (b) Ac2O, Py; (c) O3, MeOH/CH2Cl2, −78 °C; (d) NaBH4, from −78 °C to rt; (e) chromatographic separation; (f) Ac2O, Py, DMAP.
Figure 24
Figure 24
The key synthetic steps employed in the synthesis of lipiarmycins. The reaction used to build the indicated carbon–carbon single bonds, carbon–carbon double bonds, macrolactone bond, and glycosidic bonds are highlighted with blue, red, pink, and green color, respectively.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. American Chemical Society International Historic Chemical Landmarks. Discovery and Development of Penicillin. [(accessed on 28 April 2020)]; Available online: http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/fl....
    1. Aminov R. A brief history of the antibiotic era: Lessons learned and challenges for the future. Front. Microbiol. 2010;1:134. doi: 10.3389/fmicb.2010.00134. - DOI - PMC - PubMed
    1. Grasso L.L., Martino D.C., Alduina R. Production of antibacterial compounds from Actinomycetes. In: Dhanasekaran D., Jiang Y., editors. Actinobacteria-Basics and Biotechnological Applications. InTech; Rijeka, Croatia: 2016. p. Ch. 07.
    1. Ventola C.L. The antibiotic resistance crisis: Part 1: Causes and threats. Pharm. Ther. 2015;40:277–283. - PMC - PubMed
    1. Chang Q., Wang W., Regev-Yochay G., Lipsitch M., Hanage W.P. Antibiotics in agriculture and the risk to human health: How worried should we be? Evol. Appl. 2015;8:240–247. doi: 10.1111/eva.12185. - DOI - PMC - PubMed

LinkOut - more resources

  NODES
inspiration 1
INTERN 1
twitter 2