Chapter 18: Molecular biotechnology

We start this Chapter by examining the molecular aspects of antifungal agents; those that target the fungal membrane, and those that target the fungal wall. Clinical control of systemic mycoses in the 21st century is still centred on use of azoles and polyenes, but combinatorial therapy is a promising molecular approach to managing development of resistance. In the agricultural sector control of fungal disease in the 21st century is dominated by the strobilurins, fungicides produced by fungi, and integrated pest management programmes use tactics to avoid fungicide resistance very similar to those employed in combinatorial therapy.

In the rest of the Chapter we venture into territory that is more generally recognised as representing ‘molecular biology’. We discuss fungal genetic structure and the sequencing, annotation and comparison of fungal genomes. We then describe methods of manipulating genomes to enable commercial production of recombinant protein and other metabolites by filamentous fungi.

But we start this account of 21st century fungal molecular biology by looking back to the end of the 19th century, to note that Paul Ehrlich, winner of the Nobel Prize in Physiology or Medicine in 1908 (visit: https://nobelprize.org/nobel_prizes/medicine/laureates/1908/ehrlich-bio.html), developed, so long ago, the concept of selective toxicity by insisting that the chemistry of drugs used must be studied in relation to their mode of action and their affinity for the cells of the organisms against which they were directed. His aim was, as he expressed it, to find chemical substances to serve as ‘magic bullets’ which would go straight to the disease organisms at which they were aimed and do minimum damage to the diseased host.

Ehrlich’s team used the now-common approaches of screening many newly synthesised compounds for anti-microbial activity followed by optimisation of the biological activity of a lead compound through systematic chemical modifications. In 1909 the team discovered the organic arsenical compound ‘Salvarsan’ to treat syphilis; it was the 606th compound the team had synthesised for testing and was the first organic antibiotic.

Of course, thirty years after this, penicillin became the ultimate magic bullet antibacterial as the result of a chance discovery (see Section 17.15), but Ehrlich established the systematic approach that has become known as drug discovery.

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Ordering details: Moore, D., Robson, G.D. & Trinci, A.P.J. (2011). 21st Century Guidebook to Fungi. Cambridge, UK: Cambridge University Press. ISBN: 9780521186957.

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Updated September, 2018

December 23, 2016