Table Of ContentAdvances in Biochemical Engineering/Biotechnology 148
Series Editor: T. Scheper
Jens Schrader
Jörg Bohlmann Editors
Biotechnology
of Isoprenoids
148
Advances in Biochemical
Engineering/Biotechnology
Series editor
T. Scheper, Hannover, Germany
Editorial Board
S. Belkin, Jerusalem, Israel
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A.-P. Zeng, Hamburg, Germany
J.-J. Zhong, Shanghai, China
W. Zhou, Shanghai, China
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More information about this series at http://www.springer.com/series/10
ö
Jens Schrader J rg Bohlmann
(cid:129)
Editors
Biotechnology of Isoprenoids
With contributions by
Jorge Alonso-Gutierrez (cid:1) Stephen Bell (cid:1) Ralf G. Berger
Rita Bernhardt (cid:1) Jörg Bohlmann (cid:1) Albert Boronat
Joe Chappell (cid:1) Yun Chen (cid:1) Kevin W. George
Björn Hamberger (cid:1) Allison Maree Heskes (cid:1) Simon Janocha
Zuodong Jiang (cid:1) Jay D. Keasling (cid:1) Chase Kempinski
Bernd Markus Lange (cid:1) Taek Soon Lee
Robin-Hagen Leonhardt (cid:1) Yi Li (cid:1) Marco Antonio Mirata
Jens Nielsen (cid:1) Irini Pateraki (cid:1) Blaine A. Pfeifer
Manuel Rodríguez-Concepción (cid:1) Suriana Sabri
Gerhard Sandmann (cid:1) Hendrik Schewe
Claudia Schmidt-Dannert (cid:1) Daniela Schmitz (cid:1) Jens Schrader
Verena Siewers (cid:1) Dorothea Tholl (cid:1) Claudia E. Vickers
Matthias Wüst (cid:1) Philipp Zerbe (cid:1) Guojian Zhang
Yongjin J. Zhou
123
Editors
Jens Schrader Jörg Bohlmann
Bioverfahrenstechnik Michael Smith Laboratories
DECHEMA-Forschungsinstitut University of British Columbia
Frankfurtam Main Vancouver, BC
Germany Canada
ISSN 0724-6145 ISSN 1616-8542 (electronic)
Advances in Biochemical Engineering/Biotechnology
ISBN978-3-319-20106-1 ISBN978-3-319-20107-8 (eBook)
DOI 10.1007/978-3-319-20107-8
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Preface
Isoprenoids,alsoknownasterpenoids,representthelargestclassofnaturalproducts,
comprisingmorethan40,000differentstructuresfoundinallkingdomsoflife.Plants,
inparticular,arewellknowntoharboranimpressivediversityofisoprenoidswitha
widerangeofdifferentecological,physiologicalandstructuralfunctions,including
light-harvesting pigments, hormones, phytoalexins and semiochemicals, among
others. The functions of many complex plant isoprenoids, often referred to as
secondaryorspecializedmetabolites,inthenaturalworldremaintobediscovered.
Likewise,themicrobialrealmisanotherrichsourceforisoprenoidmolecules.Since
ancient times, isoprenoids have been omnipresent in people’s every day lifes and
utilized for their many different properties, for example as medicines, flavors, and
fragrances.Isoprenoidsdefinemanyoftheflavorimpressionsoffoodsandbeverages
and may help preserve them during storage. They are keyfragrance compoundsin
perfumes,andbeyondtheirfragrantpropertiesthebiologicalactivitiesofterpenoid-
richessentialoilshavebeenusedinmanytraditionalmedicines.Modernindustrial
exploitation of isoprenoids range from some high-value pharmaceuticals such as
theanticancerdrugpaclitaxel(Taxol®)tocommoncomponentsofpersonalhygiene
and cosmetic products and inexpensive antimicrobial and organic solvent-like
ingredients of household cleaners to commodity materials such as natural rubber.
Morerecently,propertiesofterpenoidsasfuelshavebeenrediscoveredandarebeing
exploredforthedevelopmentofadvancedbiofuels.
Modern biotechnological approaches, including genomics, systems metabolic
engineering and synthetic biology, along with biochemistry and chemistry, are
bringingalongadeeperunderstandingofisoprenoidbiosynthesisinnatureandare
guiding strategies to harness this knowledge for sustainable production of isopre-
noids based on renewable resources.
With the compilation of chapters published in “Biotechnology of Isoprenoids”
wesetouttocoveraratherbroadspectrumofresearchinthisfieldtoillustrateboth
thefascinatingdiversityandthegreatindustrialpotentialofthesenaturalproducts.
Given the diversity and manifold applications of isoprenoids, this volume could
only cover selected topics while inevitably missing others. Nevertheless, we hope
thisvolumewillserveasanintroductionforthosereaderswhoarenewtothefield
v
vi Preface
ofisoprenoidsandmayalsogivetheexpertreaderanup-to-dateoverviewofrecent
advances in the field. As the editors, we are grateful to so many of our highly
esteemed colleagues who accepted our invitation and generously contributed to
their time and expertise to this compilation of sixteen chapters.
The first part of the book focuses on some of the fundamentals of isoprenoid
biosynthesisinbacteria,fungiandplantsandalsooffersadeeperinsightinoneofthe
key enzyme classes involved in isoprenoid biosynthesis, plant cytochrome P450
monooxygenases.Otherimportantclassesofenzymessuchasprenyltransferasesand
terpenoidsynthasesarecoveredwithdifferentsubchaptersinseveralchaptersacross
the book. The second part addresses fundamental techniques for metabolic engi-
neeringofmicrobes,algaeandhigherplantsandalsocoversthepotentialofmicrobial
P450s for isoprenoid hydroxylation. It also includes bioprocess engineering of
microbial isoprenoid production and analytical methods for volatile isoprenoids.
The third part covers aset ofexamples for the fascinatingarena ofisoprenoid bio-
technology with emphasis on industrially important products. With ascending
number of isoprenoid C atoms in mind, the seven chapters of this part are each
devotedtoaparticularisoprenoidproductorproductclass:thehemiterpeneisoprene,
p-menthane monoterpenoids, sesquiterpenoids such as artemisinic acid, farnesene
andnootkatone,diterpenoidssuchaspaclitaxelandambroxide-relatedcompounds,
and carotenoids. The reader will also find a variety of other highly interesting
isoprenoidproductsinthecourseofthechaptersinPartsIandII.
We hope this book will provide all readers with new inspiration for their
learning, teaching and research in the field of biotechnology of isoprenoids.
May 2015 Jens Schrader
Jörg Bohlmann
Contents
Part I Biosynthesis and Function of Isoprenoids
Terpenoid Biosynthesis in Prokaryotes. . . . . . . . . . . . . . . . . . . . . . . . 3
Albert Boronat and Manuel Rodríguez-Concepción
Biosynthesis of Terpenoid Natural Products in Fungi . . . . . . . . . . . . . 19
Claudia Schmidt-Dannert
Biosynthesis and Biological Functions of Terpenoids in Plants. . . . . . . 63
Dorothea Tholl
Cytochromes P450 for Terpene Functionalisation
and Metabolic Engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Irini Pateraki, Allison Maree Heskes and Björn Hamberger
Part II Fundamental Technologies for Metabolic, Enzyme
and Process Engineering of Isoprenoids
Enabling Technologies to Advance Microbial Isoprenoid
Production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Yun Chen, Yongjin J. Zhou, Verena Siewers and Jens Nielsen
Metabolic Engineering of Higher Plants and Algae
for Isoprenoid Production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Chase Kempinski, Zuodong Jiang, Stephen Bell and Joe Chappell
Advances in the Analysis of Volatile Isoprenoid Metabolites . . . . . . . . 201
Matthias Wüst
vii
viii Contents
Terpene Hydroxylation with Microbial Cytochrome P450
Monooxygenases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Simon Janocha, Daniela Schmitz and Rita Bernhardt
Bioprocess Engineering for Microbial Synthesis and Conversion
of Isoprenoids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Hendrik Schewe, Marco Antonio Mirata and Jens Schrader
Part III From Biosynthesis to Biotechnological Production
of Selected Isoprenoids
Isoprene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
Claudia E. Vickers and Suriana Sabri
Biosynthesis and Biotechnology of High-Value p-Menthane
Monoterpenes, Including Menthol, Carvone, and Limonene. . . . . . . . . 319
Bernd Markus Lange
Isoprenoid Drugs, Biofuels, and Chemicals—Artemisinin, Farnesene,
and Beyond. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
Kevin W. George, Jorge Alonso-Gutierrez, Jay D. Keasling
and Taek Soon Lee
Nootkatone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391
Robin-Hagen Leonhardt and Ralf G. Berger
Current and Emerging Options for Taxol Production. . . . . . . . . . . . . 405
Yi Li, Guojian Zhang and Blaine A. Pfeifer
Enzymes for Synthetic Biology of Ambroxide-Related Diterpenoid
Fragrance Compounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
Philipp Zerbe and Jörg Bohlmann
Carotenoids of Biotechnological Importance. . . . . . . . . . . . . . . . . . . . 449
Gerhard Sandmann
Erratum to: Isoprenoid Drugs, Biofuels, and Chemicals—Artemisinin,
Farnesene, and Beyond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469
Kevin W. George, Jorge Alonso-Gutierrez, Jay D. Keasling
and Taek Soon Lee
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471
Part I
Biosynthesis and Function
of Isoprenoids
