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commercially for plant disease control were developed

in Japan, mainly for the control of rice diseases (rice

blast caused by Magnaporthe grisea, and rice sheath

blight, caused by Rhizoctonia solani). In addition to these

fermenter-produced antibiotics, several biological con-

trol agents are known to produce antifungal antibiotics.

But these compounds are exploited indirectly by

marketing the biocontrol agents as microbial inoculants

• a strategy that can avoid the need to undertake
  detailed and expensive toxicological testing.

The Japanese agricultural antibiotics

Five novel types of antifungal antibiotic have been

discovered and commercialized in Japan. They are dis-

cussed briefly below, and their structures are shown

in Fig. 17.10.

Polyoxins and nikkomycin

The polyoxins, including polyoxin D, are specific

inhibitors of chitin synthesis and therefore represent

a unique mode of action. Their discovery in 1965

raised hopes that they could have significant roles in

controlling fungi and insects – the two major groups

of chitin-containing organisms – while having no

effect on higher animals or plants. Nikkomycin is a

similar compound that acts in the same way. Both

compounds bind strongly to the active site of chitin

synthase, and compete with the normal substrate,

UDP-N-acetylglucosamine from which chitin is syn-

thesized (see Fig. 7.11). They have been used in prac-

tice to control some plant diseases, especially sheath

blight of rice (Rhizoctonia) and black spot of pear

(Alternaria) in Japan. However, these pathogens

rapidly develop tolerance/resistance to the antibiotics

in field conditions, because mutant strains of the

fungi show reduced antibiotic uptake. Attempts to use

these antibiotics to control diseases of human and

animal hosts have also been unsuccessful. In vitro

studies in laboratory media show that the polyoxins

are powerful inhibitors of chitin synthesis. However,

these compounds are taken into fungal cells through

membrane proteins that are normally used for the

uptake of dipeptides, and the abundance of small pep-

tides in human or animal tissues competitively blocks

the uptake of these antibiotics.

Blasticidin-S, kasugamycin, and validamycin

These three antibiotics have found limited roles in

Japanese agriculture. Blasticidin-S inhibits protein

synthesis in bacteria and a few fungi, by binding to

the large subunit of 70S and 80S ribosomes. It was

developed for control of rice blast (M. grisea) but later

it was replaced by another protein synthesis inhibitor,

kasugamycin, which has lower mammalian toxicity.

Resistance has developed to both of these compounds

in field conditions. It is based on reduced uptake of

348 CHAPTER 17

Table 17.3Some antifungal antibiotics used for the control of plant or human mycoses.

Antibiotic Produced by Fungi affected Site/mode of action

Griseofulvin Penicillium griseofulvum Many (not Oomycota) Fungal tubulins
Polyene macrolides Streptomyces spp. Many (not Oomycota) Cell membrane
Polyoxins Strep. cacaoi Many (not Oomycota) Chitin synthesis
Validamycin A Strep. hygroscopicus Some Morphogen
Blasticidin-S Strep. griseochromogenes Some Protein synthesis
Kasugamycin Strep. kasugaensis Some Protein synthesis
Streptomycin Strep. griseus Oomycota Calcium?
Pyrrolnitrin Pseudomonasspp.
Pyoluteorin Pseudomonasspp.
Gliotoxin Trichoderma virens
Gliovirin T. virens
Viridin T. virens

Implicated in biocontrol

Viridiol T. virens

Various plant by nutrient competition,

Heptelidic acid T. virens

pathogens antibiosis, parasitism of

Trichodermin Trichodermaspp.

other fungi, etc.

6-pentyl-a-pyrone Trichodermaspp.
Suzukacillin Trichodermaspp.
Alamethicine Trichodermaspp.

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