Volume 11, Part 4, November 1997

FUNGI NATURALLY FORM MANY DIVERSEBIOCHEMICAL PRODUCTS, SOME OF WHICH ARE

NOW COMMERCIALLY IMPORTANT; HOW ANDWHY DO THEY DO THIS?

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Under natural environmental conditions, or inculture, growing fungi will take from their sur-roundings those nutrients that they can use easi-ly as energy sources to produce materials such asproteins, lipids and nucleic acids, for continuedgrowth and biomass production (primary metab-olism). This allows them to proliferate andcolonise new regions to obtain more nutrients.Primary metabolites are formed during theactive growth of the fungus and these will accu-mulate in the surroundings if growth becomesrestricted or when supplies of key nutrients aredepleted. Some primary metabolites have com-mercial importance and large scale cultures aregrown industrially with the specific purpose ofobtaining large quantities of these fungal prod-ucts including organic acids such as citric acid(used in food and soft drink manufacturing),ethanol (used in alcoholic drinks production),enzymes (e.g. pectinases, glucose isomerase andlipases used in food processing) and amino acidsand vitamins (food supplements).

As nutrient depletion occurs in a particularenvironment, or in culture, growth of the fungusslows down and parts of the mycelium switch tousing different biochemical pathways. Thisalteration in metabolism prevents the fungusfrom poisoning itself and maintains the biochem-ical machinery of the cells. Primary metabolitesand intermediate compounds which have accu-mulated in the fungus are converted to differentproducts (secondary metabolites) which are notnormally made during active growth and are notessential for vegetative proliferation. Some ofthese secondary metabolites are complex mole-cules and are produced when the fungus is notactively growing; their formation may accompa-ny differentiation and sporulation in the fungus.Some are very useful economically importantproducts (e.g. antibiotics) but some are extreme-ly harmful (mycotoxins) to man and animals.

The majority of fungi produce very similar pri-

mary metabolites. These contribute to thebiosynthesis of the building blocks of fungalmycelium. Fungi are very versatile and can use arange of different sources of nutrients which areassimilated into the primary metabolic pathwaysat different points. When growth becomesrestricted by some factor, products and interme-diate compounds will then accumulate in the cul-ture medium. This can be brought about bymanipulation of the particular nutrients providedfor growth or the provision of specific environ-mental conditions. It is this attribute which isexploited for the commercial production of usefulprimary and secondary fungal products.

For example, one of the intermediate com-pounds in primary metabolism is citric acidwhich is produced commercially in large quanti-ties (several hundred thousand tons a year) usingcultures of the fungus. Aspergillus niger. On anindustrial scale high levels of glucose are provid-ed as substrate (often fed in as molasses) allow-ing the fungus to establish growth in a batchculture. The medium (pH in actively growingcultures is 5.0-6.0) is subsequently acidified toaround pH 2.0 and this limits growth. The fun-gus then converts the sugar to citric acid butbecause growth is restricted it is not metabolisedin the normal way and it accumulates in themedium. This production system is very sensi-tive to the balance of nutrients and the presenceof trace metals in the culture. If levels of iron ormanganese are too high in the medium otherproducts may be formed and accumulate inplace of citric acid, however careful control of thecultures will give rise to good yields.

Secondary metabolites are more species-spe-cific and products are often unique to a particu-lar species. For this reason it is likely thatalthough a very large number of fungal secondarymetabolites have now been identified many morewill be described in future as the activities ofmore fungal species are investigated. By manip-

ulation of the culture conditions it is possible forthe production of a secondary metabolite to beprevented or a fungus may be induced to over-produce some of these compounds. The rate ofuse of sugar in primary metabolism may reflectthe production of a primary metabolite but thisis not so for secondary metabolite production.Most secondary products are formed at the endof active growth and are derived from primaryproducts which were synthesised earlier.

The expression of the genes controlling sec-ondary metabolism is controlled by nutrient sup-ply (both the types and the quantity of nutrient)and growth rate. Nutrient limitation results inlow growth rate which favours secondary metabo-lism. If easily used carbon sources (e.g. glucose)and nitrogen sources (e.g. amino acids) are pro-vided then primary metabolism will continue orresume. Feeding compounds which aremetabolised more slowly (e.g. starch or lactose)will lead to the formation of secondary products.In some instances, the presence of particularmetals also influences secondary metabolism.Low growth rate (probably linked to nutrientsupply) is most important for secondary metabo-lism to proceed. Eventually the formation ofsecondary metabolites ceases when the enzymesresponsible for synthesis cease to function orwhen the levels of product build up and becomeself inhibitory (feed back inhibition).

Some commercially important secondaryproducts including antibiotics (e.g. penicillinfrom Penicillium chrysogenum, cephalosporinfrom Cephalosporium acremonium, griseofulvinfrom Penicillium griseofulvum) and alkaloids(Claviceps spp.) are derived from filamentousfungi and used medicinally. Benzylpenicillin isproduced by P. chrysogenum, grown on a mixtureof glucose to support growth and lactose to sup-

Volume 11,Part 4, November 1997

port secondary metabolism, with growth factorsand precursors of secondary metabolism (corn-steep liquor) and mineral salts , in large scalesubmerged culture. Alternatively a slow feed ofglucose may be used to maintain a low growthrate. Penicillin is eventually extracted from themycelium. Good understanding and carefulmanipulation of the cultural conditions isrequired because the synthetic process is sensi-tive to pH, temperature and the exact mix ofnutrients present as metabolism proceeds. Theuse of mutation and selection has gradually ledto an increase in the amounts now synthesised inindustrial culture.

Secondary metabolites are not essential forgrowth but are produced naturally by manyfungi. Many of the compounds produced haveantifungal and antibacterial activity (e.g. antibi-otics, mycotoxins) and may therefore impart acompetitive advantage, acting as weapons forsurvival. The compounds have antimicrobialactivity and producer organisms may well besensitive to these. Most have mechanisms toprevent their own demise from the effects of thecompounds they produce. In most cases theproducts are formed after active growth and bythat time the mycelium is able to detoxify thecompound or prevent entry of the antibioticthrough the cell wall by a change in the perme-ability of the plasmamembrane.

Fungi are widely used for the production ofcommercially important products and are underconstant investigation for other potentially use-ful products.

Susan IsaacSchool of Biological Sciences,

Life Sciences Building, University of Liverpool,Crown Street, Liverpool, L69 7ZB

THE BMS SLIDE COLLECTION

The Society has received a large collection of transparencies from the estate of the late Dr J. E. Milne.There are nearly 600 slides of basidiomycetes, more than 200 of myxomycetes and about 150ascomycetes. It will take some time to sort all these, evaluate them and incorporate the best in thecollection. The slide committee has not yet viewed any of them and before it does the labelling isbeing checked, and where necessary the names updated. Many of the photographs were taken over 30years ago but they have been carefully stored and seem to be in good condition.

MH

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