What is the role of microbial biotechnology and genetic engineering in medicine?

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Abstract

Microbial products are essential for developing various therapeutic agents, including antibiotics, anticancer drugs, vaccines, and therapeutic enzymes. Genetic engineering techniques, functional genomics, and synthetic biology unlock previously uncharacterized natural products. This review highlights major advances in microbial biotechnology, focusing on gene‐based technologies for medical applications.

Abstract

Microbial biotechnology, the technological application of microorganisms, has been instrumental in producing significant natural bioactive products. These include antibiotics, antifungals, anticancer drugs, antiparasitics, antivirals, immunosuppressants, toxoid vaccines, and therapeutic enzymes. Certain microbial components have proven invaluable in the creation of genetic tools, such as CRISPR‐Cas systems and thermostable DNA polymerase enzymes. These tools are essential for the development of genetic engineering strategies. Genetic engineering, as a discipline, plays a crucial role in the rational and precise advancement of microbial biotechnology. Consequently, these two conceptual themes—microbial biotechnology and genetic engineering—exhibit a positive interplay. This review presents major advancements in microbial biotechnology, with a particular emphasis on gene‐based technologies within the medical field.

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Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019

David J Newman, Gordon M. Cragg (2020)

This review is an updated and expanded version of the five prior reviews that were published in this journal in 1997, 2003, 2007, 2012, and 2016. For all approved therapeutic agents, the time frame has been extended to cover the almost 39 years from the first of January 1981 to the 30th of September 2019 for all diseases worldwide and from ∼1946 (earliest so far identified) to the 30th of September 2019 for all approved antitumor drugs worldwide. As in earlier reviews, only the first approval of any drug is counted, irrespective of how many "biosimilars" or added approvals were subsequently identified. As in the 2012 and 2016 reviews, we have continued to utilize our secondary subdivision of a "natural product mimic", or "NM", to join the original primary divisions, and the designation "natural product botanical", or "NB", to cover those botanical "defined mixtures" now recognized as drug entities by the FDA (and similar organizations). From the data presented in this review, the utilization of natural products and/or synthetic variations using their novel structures, in order to discover and develop the final drug entity, is still alive and well. For example, in the area of cancer, over the time frame from 1946 to 1980, of the 75 small molecules, 40, or 53.3%, are N or ND. In the 1981 to date time frame the equivalent figures for the N* compounds of the 185 small molecules are 62, or 33.5%, though to these can be added the 58 S* and S*/NMs, bringing the figure to 64.9%. In other areas, the influence of natural product structures is quite marked with, as expected from prior information, the anti-infective area being dependent on natural products and their structures, though as can be seen in the review there are still disease areas (shown in Table 2) for which there are no drugs derived from natural products. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully in the optimization of many recently approved agents, we are still able to identify only two de novo combinatorial compounds (one of which is a little speculative) approved as drugs in this 39-year time frame, though there is also one drug that was developed using the "fragment-binding methodology" and approved in 2012. We have also added a discussion of candidate drug entities currently in clinical trials as "warheads" and some very interesting preliminary reports on sources of novel antibiotics from Nature due to the absolute requirement for new agents to combat plasmid-borne resistance genes now in the general populace. We continue to draw the attention of readers to the recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated"; thus we consider that this area of natural product research should be expanded significantly.

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CRISPR provides acquired resistance against viruses in prokaryotes.

Rodolphe Barrangou, Christophe Fremaux, Hélène Deveau … (2007)

Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or addition of particular spacers modified the phage-resistance phenotype of the cell. Thus, CRISPR, together with associated cas genes, provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity.

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Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression.

Lei Qi, Matthew Larson, Luke A Gilbert … (2013)

Targeted gene regulation on a genome-wide scale is a powerful strategy for interrogating, perturbing, and engineering cellular systems. Here, we develop a method for controlling gene expression based on Cas9, an RNA-guided DNA endonuclease from a type II CRISPR system. We show that a catalytically dead Cas9 lacking endonuclease activity, when coexpressed with a guide RNA, generates a DNA recognition complex that can specifically interfere with transcriptional elongation, RNA polymerase binding, or transcription factor binding. This system, which we call CRISPR interference (CRISPRi), can efficiently repress expression of targeted genes in Escherichia coli, with no detectable off-target effects. CRISPRi can be used to repress multiple target genes simultaneously, and its effects are reversible. We also show evidence that the system can be adapted for gene repression in mammalian cells. This RNA-guided DNA recognition platform provides a simple approach for selectively perturbing gene expression on a genome-wide scale. Copyright © 2013 Elsevier Inc. All rights reserved.

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Author and article information

Contributors

Fernando Santos‐Beneit:

ORCID: http://orcid.org/0000-0001-7986-5557

fernando.santos.beneit@uva.es

Journal

Journal ID (nlm-ta): Microbiologyopen

Journal ID (iso-abbrev): Microbiologyopen

Journal ID (doi): 10.1002/(ISSN)2045-8827

Journal ID (publisher-id): MBO3

Title: MicrobiologyOpen

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2045-8827

Publication date (Electronic): 31 March 2024

Publication date Collection: April 2024

Volume: 13

Issue: 2 ( doiID: 10.1002/mbo3.v13.2 )

Electronic Location Identifier: e1406

Affiliations

[ ¹ ] Institute of Sustainable Processes Valladolid Spain

[ ² ] Department of Chemical Engineering and Environmental Technology, School of Industrial Engineering University of Valladolid Valladolid Spain

Author notes

[*] [* ] Correspondence Fernando Santos‐Beneit, Institute of Sustainable Processes, Dr. Mergelina s/n, Valladolid 47011, Spain.

Email: fernando.santos.beneit@ 123456uva.es

Author information

Fernando Santos‐Beneit http://orcid.org/0000-0001-7986-5557

Article

Publisher ID: MBO31406

DOI: 10.1002/mbo3.1406

PMC ID: 10982607

PubMed ID: 38556942

SO-VID: c62acfbe-34a4-4dab-9914-27af3bfd0a95

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date revision received : 26 February 2024

Date received : 12 January 2024

Date accepted : 12 March 2024

Page count

Figures: 5, Tables: 2, Pages: 31, Words: 25636

Funding

Funded by: None

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source-schema-version-number 2.0

cover-date April 2024

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.0 mode:remove_FC converted:01.04.2024

ScienceOpen disciplines: Microbiology & Virology

Keywords: antibiotics,biotechnology,cancer,genetic engineering,medicine,microbiology

Data availability:

ScienceOpen disciplines: Microbiology & Virology

Keywords: antibiotics, biotechnology, cancer, genetic engineering, medicine, microbiology

What is the role of microbial biotechnology and genetic engineering in medicine?

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Abstract

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Microbial Genomics

Most cited references 250

Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019

CRISPR provides acquired resistance against viruses in prokaryotes.

Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression.

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