Handbook of Industrial Mycology

785 Pages·2004·12.88 MB·English

by  Zhiqiang An

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Handbook of
Industrial Mycology
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MYCOLOGYSERIES
Editor
J. W. Bennett
Professor
Department of Cell and Molecular Biology
Tulane University
New Orleans, Louisiana
Founding Editor
Paul A. Lemke
1. Viruses and Plasmids in Fungi, edited by Paul A. Lemke
2. The Fungal Community: Its Organization and Role in the Ecosystem,
edited by Donald T. Wicklow and George C. Carroll
3. Fungi Pathogenic for Humans and Animals (in three parts),
edited by Dexter H. Howard
4. Fungal Differentiation: A Contemporary Synthesis, edited by
John E. Smith
5. Secondary Metabolism and Differentiation in Fungi, edited by
Joan W. Bennett and Alex Ciegler
6. Fungal Protoplasts, edited by John F. Peberdy and Lajos Ferenczy
7. Viruses of Fungi and Simple Eukaryotes, edited by Yigal Koltin
and Michael J. Leibowitz
8. Molecular Industrial Mycology: Systems and Applications
for Filamentous Fungi, edited by Sally A. Leong and Randy M. Berka
9. The Fungal Community: Its Organization and Role in the Ecosystem,
Second Edition, edited by George C. Carroll and Donald T. Wicklow
10. Stress Tolerance of Fungi, edited by D. H. Jennings
11. Metal Ions in Fungi, edited by Günther Winkelmann
and Dennis R. Winge
12. Anaerobic Fungi: Biology, Ecology, and Function,
edited by Douglas O. Mountfort and Colin G. Orpin
13. Fungal Genetics:Principles and Practice, edited by Cees J. Bos
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14. Fungal Pathogenesis: Principles and Clinical Applications, edited by
Richard A. Calderone and Ronald L. Cihlar
15. Molecular Biology of Fungal Development, edited by
Heinz D. Osiewacz
16. Pathogenic Fungi in Humans and Animals: Second Edition, edited by
Dexter H. Howard
17. Fungi in Ecosystem Processes, John Dighton
18. Genomics of Plants and Fungi, edited by Rolf A. Prade
and Hans J. Bohnert
19. Clavicipitalean Fungi: Evolutionary Biology, Chemistry, Biocontrol,
and Cultural Impacts, edited by James F. White Jr., Charles W. Bacon,
Nigel L. Hywel-Jones, and Joseph W. Spatafora
20. Handbook of Fungal Biotechnology, Second Edition, edited by
Dilip K. Arora
21. Fungal Biotechnology in Agricultural, Food, and Environmental
Applications, edited by Dilip K. Arora
Additional Volumes in Preparation
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Handbook of
Industrial Mycology
edited by
Zhiqiang An
Marcel Dekker New York
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Foreword
Theeconomicimportanceoffungiisalmostimpossibletoexaggerate.Notonlyarethey
integraltothegreatecologicalcyclesofthenaturalworld,andnotonlydotheirmycorrhizal
associationsprovidethefoundationforagricultureandforestry,theyarealsoessentialto
biotechnology.Infact,modernbiotechnologyhasitsrootsinfungalfermentations.Yeasts
have been used since antiquity in brewing and baking, while molds have been used to
improve the flavor of cheese and in the production of Asian condiments such as soy
sauce and miso. During the twentieth century, industrial fermentations were developed
for production of organic acids, diastatic enzymes, plant growth hormones, natural and
semisyntheticantibiotics,antitumoragents,andimmunomodulators.Thecommercialde-
velopment of penicillin, the first and most important of the clinically useful antibiotics,
laid the groundwork for much of what has come after, especially the technology for
growing filamentous fungi in submerged culture. With new discoveries, it has become
apparent that the potential applications of fungal metabolism are greater than we once
suspected.
TheoriginalintentoftheMarcelDekkermycologyserieswastoestablish‘‘aniche
for publication of work dealing with all aspects of mycology.’’ A volume on Industrial
Mycologyislongoverdue.Biotechnologistshavemadegreatprogressindiscoveringhow
to manipulate yeasts and molds at the biochemical and molecular level. They have ex-
ploitedtwomajorphysiologicalcharacteristicsoffungi:theirabilitytodegradesimpleand
complexpolymersandtheirabilitytobiosynthesizeahugevarietyofcomplexsecondary
metabolites. Fungi can be engineered to produce many heterologous proteins and they
remainanimportantsourceofnoveldrugs,includinganticancerdrugsandimmunefunc-
tionregulators.Severalspecies(e.g.,Saccharomycescerevisiae,Aspergillusnidulansand
Neurospora crassa) are superb models.
Thisnewvolumecoversboththeoreticalandpracticalaspectsofindustrialmycology
with emphasis on the dramatic advances in the application of bioinformatics, molecular
biology, ‘‘reverse genetics,’’ combinatorial chemistry, metabolic engineering, genomics,
proteomics,andcognatefieldstothemanipulationoffungi.Collectively,thesetechniques
have altered what is possible in the discovery laboratory.
Dividedintoeightsectionsand26chapters,IndustrialMycologyisacomprehensive
guidetothenewmycologyofthe21stcentury.Itdescribeshowfungicontributedirectly
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iv Foreword
to the contemporary pharmaceutical industry, and how they can be manipulated in order
to contribute more in the future. Dr. Zhiqiang An, editor, has done an excellent job of
bridgingthetraditionalgulfbetweenacademicandindustrialstudiesoffungi.Inaddition,
he has brought together a stellar group of international experts to write the chapters. As
a result of his efforts, IndustrialMycology presents up-to-date information on more than
twodozenseparatetopics,therebyprovidinganinvaluablereferenceforanyoneinvolved
inappliedmycology.Thisbookwillguideresearcherssothattheycanapplynewscientific
approaches for using fungi to solve many real world problems. It is intended to inspire
aswellastoinform.Thepharmacologicalpotentialoffungiisimmenseandawaitsfurther
exploitation.
J. W. Bennett
Department of Cell and Molecular Biology
Tulane University
New Orleans, Louisiana, U.S.A.
Preface
Fungiarenutrition-absorptiveeukaryoticorganismsfoundineveryecologicalniche.Be-
cause of their simplistic and rapid life cycles, yet complex genetics, metabolism, and
morphology,fungihavebeenstudiedinthelaboratoryasmodelsystems(suchasSaccharo-
myces cerevisiae, Aspergillus nidulans, and Neurospora crassa ) in every aspect of the
biological sciences. The economic importance of fungi is equally impressive, with uses
in the food and beverage industries, agriculture, the pharmaceutical and agrochemical
industries,andmedicine.Thesignificanceoffungiasbothlaboratorymodelorganismsand
industrial processes is reflected by the large number of specialized disciplines dedicated
to the study of mycology, such as plant pathology, medical mycology, food mycology,
environmental mycology, and industrial mycology. This book provides an overview of
recent developments in industrial mycology, with emphasis on discovery of bioactive
metabolites, biocatalysts, and the underlying genetics of fungi.
Fungi are of interest to the pharmaceutical and agrochemical industries because of
the diverse bioactive metabolites produced by these organisms. Since the treatment of
bacterialinfectionsusingpartiallypurifiedpenicillintwo-thirdsofacenturyago,bioactive
fungalmetaboliteshavestronglyinfluencedthedevelopmentofthemodernpharmaceutical
andagrochemicalindustries.Mevinolin,cyclosporinA,(cid:1)-lactamantibiotics,pneumocan-
dins,ergotamine,strobilurins,andmycophenolicacidareexamplesofrevolutionaryphar-
maceuticalsandagrochemicalsthathaveafungalorigin.Chapter3providesacomprehen-
sive review of the bioactive fungal metabolites discovered to date. The isolation of
sordarinsisoneexampletoillustratethecomplexityofthebioactivemetabolitediscovery
process(Chapter11).Inspiteofthesuccessofbioactivefungalmetabolitesaspharmaceuti-
calsandagrochemicals,fungiremainanessentiallyuntappedsourceofmedicinesbecause
onlyasmallfractionofthevastfungalkingdomhasbeenexploredforbioactivemetabolite
production.Thepotentialfordiscoveringnewbioactivemetabolitesfromfungiisunlim-
ited.
The industrial discovery of bioactive fungal metabolites is a complex, integrated,
but somewhat empirical process. Major steps in this process include: 1) collection and
identificationofnaturalmaterial(Chapter6);2)chemicalextraction(Chapter8);invitro
assay for biological activities (Chapter 10); 4) isolation and structural elucidation of the
activecomponentsfromtheextracts(Chapter8);5)characterizationoftheinvivobiologi-
v
vi Preface
cal efficacy andtoxicity profiles; and 6)strain and fermentation improvementfor higher
productiontiterandreductionofundesirablesideproducts(Chapters19and20).Although
one of most critical steps in fungal natural products drug discovery, in vivo biological
efficacyandtoxicityprofilingoffungalmetabolitesisnotaddressedinthisbookbecause
itismostlyamammalianclinicalissue,andnotamycologicalone,whichisthefocusof
this book.
Industrial fungalbioactive metabolitediscovery has beenlargely anempirical pro-
cess and this empirical approach has been and will continue to be effective. However,
recentadvancesinthegeneticsofmicrobialsecondarymetabolitebiosynthesis,genomics,
andmetabolicengineeringwillplayanever-increasingroleinfacilitatingfungalbioactive
metabolitesdiscovery.Thisbookattemptstoprovidereaderswithcomprehensivediscus-
sions on the genetics of fungal secondary metabolism (Chapters 12B18). Another major
advanceinfungalbioactivemetabolitediscoveryliesindetectionandpredictionmethods,
such as chemometric and genetic methods (Chapter 9). Genetic engineering will also
help to expand the recovery of bioactive metabolites and enzymes from unculturable
and difficult-to-grow fungi by expressing secondary metabolite-encoding and enzyme-
encoding genes and gene clusters in heterologous hosts (Chapter 7).
Toserveasastand-alonereferencebook,overviewsofindustrialmycology(Chapter
1), the fungal kingdom (Chapter 2), fungal cell cycle control (Chapter 4), and fungal
genetictransformation(Chapter5)areincluded.Severalchaptersaddressingotherindus-
trial mycology topics are also included: industrial fungal bioconversions (Chapter 21),
metabolomics(Chapter22),engineeringoffungalmetabolicbiosyntheticpathways(Chap-
ter 23), heterologous protein and enzyme expression in fungi (Chapter 24), mycotoxin
(Chapter 25), and fungi as biocontrol agents (Chapter 26).
Finally,IwouldliketoexpressmygratitudetoDr.JoanBennettfortheopportunity
tocontributetotheMycologyseries,andIamindebtedtotheexpertauthorswhoagreed
to contribute to this endeavor. I also want to thank Ms. Anita Lekhwani and Joseph
Cacciottoli of Marcel Dekker, Inc., for their dedicated assistance throughout the project.
Zhiqiang An