Chapter 18: Molecular biotechnology
Mycology is a curious discipline. A peculiar division has arisen in what the word means because its meaning seems to depend on who you are. Around the world, biochemists, molecular biologists and even clinical scientists study fungi in great detail, but don’t call themselves mycologists. They call themselves biochemists, molecular biologists or clinicians! Yet they study only fragments of the organism. If the molecular biology (or biochemistry, or pathology) is to be properly understood and exploited then at some stage those fragments have to be assembled into an overall, whole organism, view. At which point we are in danger of needing one of those ‘field mycologists’ that are so undervalued that: ‘In many parts of the world mycologists are an endangered species’ (Minter, 2001) and consideration needs to be given to ‘… promoting the conservation of taxonomists themselves’ (Courtecuisse, 2001).
In this textbook we have attempted to provide the overall view of each topic from the start; we like to think of this as the real fungal biology. Now, in this chapter, it is time to be divisive. Throughout this book we have attempted to provide molecular details and molecular interpretations of as many as possible of the situations we have described. Knowing what we know by this stage about the overall biology of fungi we can afford to examine some of the fragments in much more detail and ask how they can be manipulated to our advantage.
We start the Chapter by examining the molecular aspects of antifungal agents; those that target the membrane, and those that target the wall. Clinical control of systemic mycoses at the start of 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 mycocides at the start of the 21st century are dominated by fungicides produced by fungi: the strobilurins.
In the rest of this Chapter we venture into territory that is more generally recognised as representing ‘molecular biology’. We discuss fungal genetic structure; sequencing fungal genomes; and annotating the genome. We then make a comparison of fungal genomes and describe methods of manipulating genomes: targeted gene disruption, transformation and recombinant vectors; all of which contribute to developing techniques that enable recombinant protein production by filamentous fungi.
In the last three sections we describe specific examples of other aspects of bioinformatics (the manipulation of very large data sets) in mycology. First, that comprehensive genomic data mining supports the notion that there are different developmental control mechanisms in fungi, animals and plants. Second, that the effects of climate change on fungi can be revealed by analysis of large survey data sets. Third, and finally, that mathematical modelling and computer simulation of hyphal growth based on the understanding of hyphal growth kinetics presented in Chapter 4 gives rise to a computer program that produces highly realistic cyberfungi ‘growing’ on the monitor screen.
We start this account of 21st century fungal molecular biology by turning back to the end of the 19th century, noting that Paul Ehrlich, winner of the Nobel Prize in Physiology or Medicine in 1908 (visit: http://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 December 23, 2016