Daniel Mavu
University of Namibia, Namibia
Title: A review of rise of modern pharmaceutical biotechnology in antibiotic drug discovery and development from natural sources and future implications
Biography
Biography: Daniel Mavu
Abstract
Background: In the context of antibiotic research and development (R&D), Biotechnology is the exploitation of biological processes for
industrial production. Early antibiotic biotechnology relied on empirical research whereas modern biotechnology is regarded as having
started in 1973 with the discovery of recombinant DNA technology. Currently, two thirds of antibiotics in clinical use globally are of
natural microbial origin, and were developed through these same empirically derived techniques. Empirical antibiotic R&D from natural
sources (NS) was, however, not sustainable. No new classes of antibiotics were discovered until after 2000 when there was renewed
interest in antibiotic R&D from NS, this time powered by advances in biotechnology. Unfortunately, there are currently no comprehensive
systematic reviews of the technologies, focus areas of antibiotic R&D and outcomes thereof over the years. This review aims to highlight
the most important developments, and contributions in antibiotic discovery and development from natural sources (NS).
Methods: A systematic literature review design was adopted for the review. Publications on R&D on antibiotics and biotechnology
were retrieved from research databases including science direct, PubMed, Medline and open source databases like google scholar.
The search terms included “antibiotics and biotechnology, research and development, methods and production.” The main outcome
variables were trends, advances and contributions of biotechnology used for R&D of novel antibiotic classes/types. The study included
publications that are peer reviewed and that give antibiotic outcomes with market authorization. Data was analyzed thematically and
results are descriptively reported. Antibiotic innovations were ranked using a criteria assessing the significance of contribution to
clinical practice and future applicability to R&D of novel antibiotics from NS as well as applicability to other biomedical sciences.
Results: Out of the 126 articles retrieved from the literature (1928 – 2017), 47 studies met the inclusion criteria. Fifteen (15) articles
were excluded due overlap of information. Out of the 32 articles reviewed, 25 innovations in biotechnology had impact on R&D of
novel antibiotics in clinical use. The main trends in antibiotic R & D were in four eras: 1928-mid 1940s – the primordial era, an initial
phase when the first antibiotics were discovered without clinical use and no mass production; 1944 - 1962 is era when most antibiotics
currently in clinical use were discovered and when mass production started. Twenty (20) new classes of antibiotics were discovered and
are still used in clinical practice; 1962 – 2000 there were no innovations in new classes of antibiotics but rather synthetic modifications
of existing compounds. The era of high discoveries of antibiotics was referred to as the golden era 1944-1970; the rise in antimicrobial
resistance due to over use of antibiotics led to combinatorial techniques for novel synthetic antibiotics in the 1980s with no new classes;
in 1990’s genomic era – the biotechnological advances in genome sequencing led to innovations of antibiotics discovery based on
high throughput screens of existing compound libraries to identify targets as well as the genes encoding. Unfortunately the yield for
antibiotics based on genomic sequencing remained poor and because of these disappointments, interest in antibiotics from NS was
revitalized in the 2000’s renascence era, using advanced biotechnology. This led to two new classes of novel antibiotics being marketed
by 2010 and two more were still in phase I of the pipeline. A small number were in the preclinical phases.
Conclusion: A combination of advanced biotechnology applied on NS alongside synthetic modifications has the highest potential for
R&D of novel antibiotics. The future focus areas for antibiotic R&D from NS will focus on the 99% non-culturable microorganism
that have not been exploited, on R&D all microbes with silent genes with potential, R&D on microbes from unexplored environments
and R&D on non-multiplying microorganisms.