27 - 29 June 2022, Edinburgh, UK Directing Biosynthesis VI
27 - 29 June 2022, Edinburgh, UK Directing Biosynthesis VI #DBVI
Book of Abstracts
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Welcome
Dear Colleague A very warm welcome to Directing Biosynthesis VI. On behalf of the Scientific Committee, I’d like to thank you all for taking part in what I am sure will be an exceptionally stimulating and enjoyable three days! As we all know, specialised metabolites produced by microorganisms and plants have inspired the development of many blockbuster drugs, crop protection agents and other high value chemicals. Research on the biosynthesis of such metabolites is not only of strategic importance commercially - it is also relevant to wider society and continues to play a key role in addressing emerging global challenges in health, the environment and sustainability. This year’s Directing Biosynthesis conference is the sixth in the series. The first conference was held in Cambridge in 2006 and followed on from earlier meetings focused more specifically on polyketide biosynthesis. We originally planned to hold this sixth edition in June 2020 but were forced to postpone it due to the COVID pandemic. In the interim, we held a two-day online meeting (in April 2021), which proved to be an excellent forum for disseminating the latest advances in the field despite the difficult circumstances most of us were enduring at that time. Modern biosynthesis research is exceptionally interdisciplinary, employing a wide range of techniques from diverse fields, including (meta)genomics, molecular genetics, enzymology, structural biology, ecology, evolutionary biology, organic synthesis, analytical chemistry, and synthetic biology. The ongoing success of this conference series serves to highlight the impact of our efforts as a community in this exciting field of contemporary science. Doubtless this year’s meeting will provide ample opportunity for attendees to discuss their work and initiate or renew productive collaborations. I hope you enjoy the mix of presentations, not only the keynote and contributed lectures, but also the wide range of posters and I really hope that this meeting will provide an opportunity for early career researchers to share their ideas and enthusiasm. I would like to extend thanks to all the sponsors, supporters and co-organizers who have promoted and supported this event. I strongly encourage all participants to take the opportunity to meet with members of these organizations over the next three days and learn about how we can work together to continue advancing this very exciting field. Finally, I am particularly grateful to colleagues both on the Scientific Committee and at the Royal Society of Chemistry (RSC) for their many and varied contributions to making this conference happen. Greg Challis Chair of Scientific Committee University of Warwick / Monash University
Meeting Information
Directing Biosynthesis VI is hosted by the Chemistry Biology Interface Division (CBID) of the Royal Society of Chemistry. www.rsc.org/CBID This book contains abstracts of the oral and poster presentations to be presented at the conference. All abstracts in this book are reproduced directly from typescripts supplied by the authors. Copyright remains with the authors.
Lectures All lectures will take place in the Pentland Suite, John McIntyre Conference Centre (1st Floor).
Catering Please refer to programme for catering locations.
Conference Dinner The dinner will be held on the evening of Tuesday 28 June and will take place at the Royal Botanic Garden Edinburgh from 19.00 Transport will be provided, please check at the registration desk for times. The cost of the dinner is included in the registration fee for in person delegates, if you are no longer able to attend please let us know.
Posters These will be on display throughout the conference in South Hall, a short walk from the main conference centre
Posters have been numbered consecutively: P01-P99 The poster sessions will take place in South Hall Monday June 27 , 15:10 – 16:20 (even numbers) and 18:00 – 19:00 (all posters) Tuesday June 28 , 13:00 – 15:00 (odd numbers)
The posters will be available to view throughout the discussion by clicking on the link in the virtual lobby. If you are an online poster presenter, please ensure that you are logged into the poster room assigned to your poster number in the lobby. Posters with a F will be presented during the flash poster presentations, taking place before the poster sessions.
Student Poster Prizes
Kindly sponsored by:
Sponsors and Exhibitors
Exhibitor
Isomerase is one of the UK’s leading biotechnology service providers and has been supporting partners for over 10 years. We combine cutting-edge synthetic biology, advanced strain bioengineering, process development and biosynthetic chemistry to create highly productive strains, and efficient cost-effective routes to commercially attractive products. For customers working with microbial products and processes in a wide variety of sectors, Isomerase offers flexible and agile biotechnology services for those partners looking for more than just a CRO.
Sponsor
NCIMB curates a unique collection of microorganisms with a host of potential industrial applications, as well as providing laboratory services, microbial identification, whole genome sequencing, microbial community analysis, qPCR and storage services. We also work collaboratively with other organisations to unlock value from microorganisms.
Scientific Committee
Professor Greg Challis (Chair) University of Warwick, UK and Monash University, Australia
Professor Sarah Barry Kings College London, UK
Professor Dominic Campopiano University of Edinburgh, UK
Professor Hai Deng University of Aberdeen, UK
Professor Kira Weissman University of Lorraine, France
Speakers
Ikuro Abe, Ph. D. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan Ikuro Abe is Professor of Natural Products Chemistry at Graduate School of Pharmaceutical Sciences, The University of Tokyo (2009-). He received his B.S. (1984) and Ph.D. (1989) from The University of Tokyo. After two years postdoctoral research with Professor Guy Ourisson at the CNRS Institut de Chimie des Substances Naturelles, and mostly with Professor Michel Rohmer at the Ecole Nationale Supérieure de Chimie de Mulhouse in France (1989-1991), he moved to the USA to work with Professor Glenn D. Prestwich at the State University of New York at Stony Brook (1991-1996) and then at The University of Utah (1996-1998). His research interests mostly focus on exploring and engineering the natural products biosynthesis. He has authored 200+ publications including Nature, Nat. Chem. Biol., Nat. Commun., JACS, ACIE, and PNAS. He received the Pharmaceutical Society of Japan Award in 2019, and Prizes for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology, Japan. He is a former President of The Japanese Society of Pharmacognosy.
Squire J. Booker Pennsylvania State University, USA
Squire J. Booker is an Evan Pugh Professor of Chemistry and of Biochemistry and Molecular Biology, and the Eberly Family Distinguished Chair in the College of Science at the Pennsylvania State University. He is also an investigator of the Howard Hughes Medical Institute. He received a B.A. degree with a concentration in chemistry from Austin College in 1987 and a Ph.D. in biochemistry from the Massachusetts Institute of Technology in 1994. After postdoctoral studies in Paris, France and at the University of Wisconsin, he joined the faculty at Penn State in 1999. Booker’s research focuses on natural product biosynthesis, antibiotic resistance and metalloenzymology, with a particular emphasis on the methylation and sulfhydrylation of unactivated carbon centers.
David Craik, FAA, FRS The University of Queensland, Brisbane, Australia
David Craik, FAA, FRS, is a group leader and Professor of Chemistry at the Institute for Molecular Bioscience at The University of Queensland, Brisbane, Australia. He obtained his PhD in organic chemistry from La Trobe University in Melbourne, Australia and undertook postdoctoral studies at Florida State and Syracuse Universities before taking up a lectureship at the Victorian College of Pharmacy in 1983. He was appointed Professor of Medicinal Chemistry and Head of School in 1988. He moved to University of Queensland in 1995 to set up a new biomolecular NMR laboratory and is currently the Director of the Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science. His research focuses on applications of cyclic peptides, toxins and NMR in drug design. He is a Fellow of the Royal Society and a Fellow of the Australian Academy of Science, is author of more than 750 papers and has trained 70 PhD students.
Dr. Ania Fryszkowska Director of Biocatalysis in Process R&D Enabling Technologies, USA
Dr. Ania Fryszkowska the Director of Biocatalysis in Process R&D Enabling Technologies at Merck Sharp and Dohme, USA, where she is responsible for driving the application of enzymes to support the drug pipeline from discovery to commercial launch. Ania received her Ph. D. in organic synthesis from the Warsaw University of Technology and then went on to complete post-doctoral studies with Professor Nigel Scrutton at the University of Manchester working on flavin-dependent enzymes. After five successful years at Dr. Reddy’s Laboratories in the UK, she joined the Biocatalysis group at Merck in 2015, where she has played a pivotal role in driving innovation and expanding biocatalytic tools for process and medicinal chemistry. Ania co-led the development of the novel nine-enzyme cascade process for islatravir (Science, 2019), focusing on the sugar portion. She was a key contributor to inventing the suite of enzymatic methods for site-selective protein functionalization, utilized in the syntheses of insulin bioconjugates MK-5160 and MK-1029 (Science, just accepted). She authored over 25 publications and patents and her scientific contributions were recognized by many awards, including the ACS Young Investigator Award in 2020. Ania co-organized a series of Virtual Biocatalysis and Protein Engineering Meet-ups, which served as a platform for early-career scientists from industry and academia to share their science during the pandemic. Christian Hertweck Leibniz Institute for Natural Product Research and Infection Biology (HKI), Germany Christian Hertweck is the Head of Department Biomolecular Chemistry and Deputy Director at the Leibniz Institute for Natural Product Research and Infection Biology (HKI), and a Full Professor in the Faculty of Biological Sciences at the Friedrich Schiller University Jena. His research focuses on the discovery of microbial natural products, elucidating and harnessing their biosynthesis (genome mining, pathway engineering), and studying the molecular basis of microbial interactions. In recognition of his group’s contribution to the field he was granted numerous awards including the Gottfried Wilhelm Leibniz Prize, and was elected as member of the German National Academy (Leopoldina) in 2015.
Timm Maier University of Basel, Switzerland
Timm Maier studied Biochemistry at the University of Tübingen, Germany, and completed his Doctorate in Structural Biology with Wolfram Saenger at Freie Universität, Berlin, Germany, in 2003. Timm Maier then moved as a Postdoc to the lab of Nenad Ban at ETH Zurich, Switzerland, where he was promoted to a team leader and lecturer position in 2006. In 2011, Timm Maier moved to the Biozentrum of the University of Basel as tenure track Assistant Professor and is Associate Professor of Structural Biology at Biozentrum since 2016. He and his team are best known for structural studies on giant multienzymes, in particular fatty acid and polyketide synthases, as well as on metabolic regulation and mTOR complexes.
Martin Schmeing Yale University, USA
Martin performed graduate research with Tom Steitz at Yale University, studying the architecture and mechanism of the large ribosomal subunit. He then performed postdoctoral training at the LMB, Cambridge, with Venki Ramakrishnan, using cryo- EM and X-ray crystallography to investigate initiation and elongation of translation. Martin established his own laboratory at McGill University in 2010, where he studies nonribosomal peptide synthetases (NRPSs). Two aspects of particular focus of the group’s NRPS research are the catalytic event which links substrate building blocks into peptide products, and the manner in which these enzymes’ domains and modules work together in a complicated and productive catalytic cycle. Martin is currently an Associate Professor of the Department of Biochemistry, the Director of the McGill Centre for Structural Biology, an Associate Director of the McGill Facility for EM Research and the Canada Research Chair in Macromolecular Machines.
Ren Xiang Tan Nanjing University, China
China Pharmaceutical Univ. (BS 1983, MS 1986), Lanzhou Univ. (Ph D 1990, Prof. Z. J. Jia), Technical Univ. Berlin (Visiting Ph D candidate, 1989-1990, Prof. F. Bohlmann), Univ. Lausanne (Visiting scholar, 1995 and 1997, Prof. K. Hostettmann), Univ. California San Diego (Visiting scholar, 2001 and 2003, Prof. W. Fenical), Nanjing Univ. (Associate Prof., 1992; Prof., 1994-present), Nanjing Univ. of Chinese Medicine (Chair Prof., 2016-present; Vice-president, 2016-2018). He works on the discovery and biosynthesis of symbiont- derived bioactive natural products. Yi Tang Penn State University, USA Yi Tang received his undergraduate degree in Chemical Engineering and Material Science from Penn State University. He received his Ph.D. in Chemical Engineering from California Institute of Technology under the guidance of Prof. David A. Tirrell. After NIH postdoctoral training in Chemical Biology from Prof. Chaitan Khosla at Stanford University, he started his independent career at University of California Los Angeles in 2004. He is currently a professor at the Department of Chemical and Biomolecular Engineering at UCLA, and holds joint appointments in the Department of Chemistry and Biochemistry; and Department of Bioengineering. His awards include the ACS Arthur C. Cope Scholar Award (2012), the EPA Presidential Green Chemistry Challenge Award (2012), NIH DP1 Director Pioneer Award (2012) and the ACS Eli Lilly Award in Biological Chemistry (2014)
Professor Chris Willis University of Bristol, UK
Chris Willis is currently Head of the Organic and Biological Chemistry Section at the University of Bristol. Her collaborative research programmes focus on the use of both synthetic biology and organic synthesis to elucidate and manipulate biosynthetic pathways to deliver novel bioactive compounds and biocatalysts, leading to >170 publications. She was awarded the RSC Flintoff Medal in 2008, was a member of the Bristol Polyketides Group awarded the 2013 Rita and John Cornforth Award and recently was recognised by an IUPAC 2019 Distinguished Women in Chemistry or Chemical Engineering Award.
Wenjun Zhang University of California, USA
Wenjun Zhang is an Associate Professor in the Department of Chemical and Biomolecular Engineering at University of California Berkeley and the Charles R. Wilke Endowed Chair in Chemical Engineering. She did her doctoral training with Yi Tang at UCLA and her postdoctoral training with Christopher T. Walsh at Harvard Medical School before joining UC Berkeley in 2011. She is the author of 70+ scientific publications and received awards such as Pew Scholar (2012), NIH Director’s New Innovator (2015), Sloan Research Fellow (2016), American Cancer Society Research Scholar (2017), Presidential Early Career Award for Scientists and Engineers (2019), etc. Zhang Lab is broadly interested in natural product discovery, biosynthesis, engineering, and biological studies.
Programme
Monday 27 June 2022 (all timings are BST)
Registration and refreshments (Lunch available from 12:00) JMCC
11:00
Welcome and introduction Greg Challis University of Warwick
12:50
Session 1: Fungal natural products Session chair: Kira Weissman
Genome mining for unknown unknowns in fungi Yi Tang UC Los Angeles, USA
13:00
K01
Structural studies of transient and higher-order interactions in polyketide synthases Timm Maier University of Basel, Switzerland Identification and characterization of bifunctional fungal terpene synthases Jaclyn Winter University of Utah, USA
13:40
K02
14:20
C01
Flash poster presentations (even numbers)
14:40
Poster session (even numbers) and refreshments South Hall
15:10
Session 2: Peptide Biosynthesis Session chair: Hajo Kries
Structures and functions of nonribosomal and non-nonribosomal peptide synthetases Martin Schmeing McGill University, Canada Structure and function of a peptide crosslinking P450 from biarylitide biosynthesis Max Cryle Monash University, Australia
16:20
K03
17:00
C02
Iterative peptide backbone N-methylation in borosin RiPP biosynthesis Michael Freeman University of Minnesota, USA
17:20
C03
17:40 Investigating the mechanisms of lanthipeptide biosynthesis using structural mass spectrometry Chris Thibodeaux McGill University, Canada C04
Poster session (all posters) and wine reception South Hall
18:00
19:00
Close of sessions
Programme
Tuesday 28 June 2022 (all timings are BST)
Session 3: Biosynthetic engineering I Session chair: Sacha Pidot
Repurposed biocatalysts for the assembly of antibiotics and toxins Christian Hertweck Leibniz Institute for Natural Product Research and Infection Biology (HKI), Germany Engineering of polyketide synthase leads to ‘low-fat’ stambomycins Su Li** Max-Planck-Institute for Terrestrial Microbiology, Germany
09.00
K04
09.40
C05
10.00 CRISPR-Cas9 in vivo editing enables rapid engineering of a complex antibiotic assembly line Wei Li Thong University of Manchester, UK
C06
Towards new more efficient and clinically relevant lincosamide antibiotics Zdenek Kamenik Institute of Microbiology Czech Acad Sci, Czech Republic
10.20
C07
Refreshments South Hall Kindly sponsored by:
10.40
Session 4: Unusual C-C bond forming enzymes Session chair: Sarah Barry
New insights into cobalamin-dependent methyltransferase reactions Squire Booker** Pennsylvania State University, USA Biosynthesis of the unusual carbon skeleton of nocuolin A T eresa Patricia Martins CIIMAR, Portugal
11.10
K05
11.50
C08
12.10 Enzymatic assembly of the salinosporamide gamma-lactam-beta-lactone anticancer warhead Katherine Bauman University of San Diego, USA
C09
Flash poster presentations (odd numbers)
12.30
** presenting online
Programme
Tuesday 28 June 2022 (all timings are BST)
Poster session from 14:00 (odd numbers) and lunch Session to include any online-only posters in addition to in-person South Hall
13:00
Session 5: Polyketide biosynthesis in Gram-negative bacteria Session chair: Jeroen Dickschat
Combining organic synthesis and synthetic biology to explore and exploit polyketide biosynthesis Chris Willis University of Bristol, UK Unveiling the iterative programming of the zeamine II enzymatic assembly line Sophie Dekimpe KU Leuven, Belgium
15.00
K06
15:40
C10
Modular α-hydroxylation in trans-AT PKSs Franziska Hemmerling ETH Zürich, Switzerland
16:00
C11
Refreshments South Hall
16.20
Session 6: Plant natural products Session chair: Stefan Schulz
16:50 Biosynthetic pathways of cyclotides- ultrastable cyclic peptides from plants with applications in agriculture and medicine David Craik University of Queensland, Australia K07
Deciphering quassinoid biosynthesis in the invasive tree of heaven (Ailanthus altissima) Jakob Franke Leibniz University Hannover, Germany Omics approaches to harness daphniphyllum alkaloid diversity Benjamin Lichman University of York, UK
17:30
C13
17:50
C14
18:10
Close of sessions
18:30
Coaches leave for Conference Dinner
19:00 Conference dinner – Royal Botanic Garden Edinburgh
Programme
Wednesday 29 June 2022 (all timings are BST) Session 7: Discovery and biosynthesis of nitrogenous metabolites Session chair: Hai Deng
NAD as a building block in natural product biosynthesis Ikuro Abe University of Tokyo, Japan
9:00
K08
TBC Ren Xiang Tan** Nanjing University, China
9:40
K09
Exploring new biocatalysts for the sphingolipid synthesis in actinobacteria Gustavo Perez-Ortiz The University of Edinburgh, UK Pseudomonas pan-genomic analysis informs the discovery of plant pathogen inhibitors Andrew Truman John Innes Centre, UK
10:20
C15
10:40
C16
11:00 Refreshments South Hall Session 8: Biosynthetic engineering II Session chair: Dominic Campopiano
Enzymatic routes to the next generation therapeutics Anna Fryszkowska Merck Sharp & Dohme, USA
11:30
K10
Simulation-guided redesign of terpene synthase product outcome Marc Van der Kamp University of Bristol, UK
C17
12:10
Enzymatic methylation in engineered biosynthetic pathways as a tool for product diversification Kristina Haslinger Rijksuniversiteit Groningen, Netherlands Fatty acid synthases (FASs) enable access to new-to-nature compounds Martin Grininger Goethe University Frankfurt, Germany
12:30
C18
12.50
C19
Lunch South Hall
13.10
Round table discussions for early-career researchers Informal discussions over lunch focusing on career directions, different systems, challenges and skills, with advice from scientists in academia and industry
13:40
Session 9: New frontiers Session chair: Greg Challis
Biosynthesis of unusual functionalities in natural products Wenjun Zhang UC Berkeley, USA Closing remarks and presentation of poster prizes Greg Challis, University of Warwick Kindly sponsored by:
14:40
K11
15.20
15.30 Close - refreshments available - JMCC
** presenting online
Keynote presentations
K01
Genome mining for unknown unknowns in fungi Yi Tang University of California, Los Angeles, USA
K02
Structural studies of transient and higher-order interactions in polyketide synthases Timm Maier Biozentrum, University of Basel, Switzerland
K03
Structures and functions of nonribosomal and non-nonribosomal peptide synthetases
Martin Schmeing McGill, Canada
K04
Repurposed biocatalysts for the assembly of antibiotics and toxins Christian Hertweck Leibniz Institute for Natural Product Research and Infection Biology (HKI), Germany New insights into cobalamin-dependent methyltransferase reactions Squire Booker Penn State University, USA Combining organic synthesis and synthetic biology to explore and exploit polyketide biosynthesis Chris Willis University of Bristol, UK Biosynthetic pathways of cyclotides- ultrastable cyclic peptides from plants with applications in agriculture and medicine Daivd Craik University of Queensland, Australia
K05
K06
K07
K08
NAD as a building block in natural product biosynthesis Ikuro Abe The University of Tokyo, Japan
K09
TBC Ren Xiang Tan Nanjing University, China
K10
Enzymatic routes to the next generation therapeutics Ania Fryszkowska Merck Sharp & Dohme, USA Biosynthesis of unusual functionalities in natural products Wenjun Zhang UC Berkeley, USA
K11
Oral presentations
C01
Identification and characterization of bifunctional fungal terpene synthases Jaclyn Winter University of Utah, USA Structure and function of a peptide crosslinking P450 from biarylitide biosynthesis Max Cryle Monash University, Australia Iterative peptide backbone N-methylation in borosin RiPP biosynthesis Michael Freeman University of Minnesota, USA
C02
C03
C04
Investigating the mechanisms of lanthipeptide biosynthesis using structural mass spectrometry
Christopher Thibodeaux McGill University, Canada
C05
Engineering of polyketide synthase leads to ‘low-fat’ stambomycins Li Su Max-Planck-Institute for Terrestrial Microbiology, Germany CRISPR-Cas9 in vivo editing enables rapid engineering of a complex antibiotic assembly line Wei Li Thong University of Manchester, UK Towards new more efficient and clinically relevant lincosamide antibiotics Zdenek Kamenik Institute of Microbiology Czech Acad Sci, Czech Republic Biosynthesis of the unusual carbon skeleton of nocuolin A Teresa Patricia Martins ICBAS, Portugal Enzymatic assembly of the salinosporamide gamma-lactam-beta-lactone anticancer warhead Katherine Bauman The Regents of the Univ. of Calif., USA
C06
C07
C08
C09
C10
Unveiling the iterative programming of the zeamine II enzymatic assembly line Sofie Dekimpe KU Leuven, Belgium
C11
Modular α-hydroxylation in trans-AT PKSs Franziska Hemmerling ETH Zürich, Switzerland
C13
Deciphering quassinoid biosynthesis in the invasive tree of heaven (Ailanthus altissima) Jakob Franke Leibniz University Hannover, Germany OMICS approaches to harness daphniphyllum alkaloid diversity Benjamin Lichman University of York, UK Exploring new biocatalysts for the sphingolipid synthesis in Actinobacteria Gustavo Perez Ortiz The University of Edinburgh, UK Pseudomonas pan-genomic analysis informs the discovery of plant pathogen inhibitors Andrew Truman John Innes Centre, UK Simulation-guided redesign of terpene synthase product outcome Marc Van der Kamp University of Bristol, UK Enzymatic methylation in engineered biosynthetic pathways as a tool for product diversification Kristina Haslinger Rijksuniversiteit Groningen, Netherlands Fatty acid synthases (FASs) enable access to new-to-nature compounds Martin Grininger Goethe University Frankfurt, Germany
C14
C15
C16
C17
C18
C19
Poster presentations
P01
Fischerazoles A-C, cyanobacterial polychlorinated lipids featuring fatty acyl chain rearrangement Kathleen Abt CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, Portugal
P02F
The evolution of glycopeptide antibiotics Martina Adamek University of Tuebingen, Germany
P03
Study of the mechanism of action and biosynthesis of microbial secondary metabolites Duha Alkhder The University of Warwick, UK
P04
A versatile spirotetronate cyclase Jawaher Alnawah University of Bristol, UK
P05F
Application of Acyl-S-acetylcysteamine (Acyl-SNAC) thiosters as synthetic mimic in biosynthetic intermediates acyl- CoAs Saad Alrashdi University of Aberdeen, UK Producing engineered lipopeptides via the ribosomal route Nina Bösch ETH Zürich, Switzerland Chloro-methoxy-tryptophan biogenesis during NRP biosynthesis Michael Brigham University of Leeds, UK Bacterial endosymbionts protect beneficial soil fungus from nematode attack Hannah Büttner Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Germany
P06
P07F
P08F
P09F
Discovery and heterologous expression of new microviridins from a Portuguese Culture Collection
Raquel Castelo-Branco CIIMAR/FCUP, Portugal
P10
Identification of the biosynthetic gene cluster for the antiviral spirotetronate MM46115, and investigation of a putative diene forming dehydratase domain Rebecca Clayton University of Warwick, UK Discovery of demurilactone A; a novel growth inhibitor of L-form Bacillus Subtilis Yousef Dashti Newcastle University, UK Engineering a bacterial biosynthetic pathway for the synthesis of novel anticancer agents Dries De Ruysscher KU Leuven - VIB Center for Microbiology, Belgium α-Methylenation of metabolic aldehydes via a biocompatible aldol condensation Jonathan Dennis University of Edinburgh, UK Structural basis of the specificity of amidinohydrolases involved in the final steps of the biosyntheses of large linear and cyclic polyketides Marcio DIAS University of Sao Paulo, Brazil Exploring the role of nonribosomal peptides in vaginal communities Jelle Dillen University of Antwerp, Belgium Chemical and enzymatic macrocyclisation of antibiotic peptides Yaoyu Ding King’s College London, UK
P11
P12
P13
P14
P15F
P16F
P17
Illuminating and exploiting programmed O-methylation in trans-AT polyketide synthases James Duncan University of Warwick, UK Exploring the natural diversity of acyltransferases producing gene- encoded lipopeptides. Johannes Eckert ETH Zürich, Switzerland Characterization of the antipathogenic molecules of lactobacilli in vegetable fermentations Tom Eilers Uantwerpen, Belgium Transformation associated recombination (TAR) cloning of promising antibiotic producing biosynthetic gene clusters (BGCs) Fayrouz El Maddah University of Warwick, UK Opening the circle – characterisation of a unique esterase in faulknamycin biosynthesis Asif Fazal University of Leeds, UK Thioesterase-mediated O-acetylation and double bond formation in peloruside biosynthesis Amy Fraley Eidgenössische Technische Hochschule Zürich, Switzerland Engineering microcin J25 for new biological activities and therapeutic applications Hans Gerstmans KU Leuven - VIB, Belgium The genetic basis of biosynthesis and anti-inflammatory activity of calendula officinalis triterpene fatty acid esters Daria Golubova Earlham Institute, UK
P18
P19
P20
P21
P22F
P23
P24F
P25
Investigating bioactive natural products from the fungus Escovopsis weberi Claudio Greco John Innes Centre, UK Adenylation domain substrate selectivity in fungal nonribosomal peptide biosynthesis Stephanie Heard University of Utah, USA Investigation of the release and cyclisation steps from the PKS-NRPS hybrid during the biosynthesis of cytochalasans Henrike Heinemann University of Hanover, Germany Small molecule discovery from LC-MS data with metaboseek Maximilian Helf Boyce Thompson Institute / Cornell University, USA Investigation of RiPPs originating from two-domain precursors Jethro Hemmann Leibniz Institute for Natural Product Research and Infection Biology - HKI, Germany Discovery of fungal depsipeptide based on a synthetic biology-based approach Yuto Homma Tohoku University, Japan Using branch point inventories to identify new biosynthetic pathways Geoff Horsman Wilfrid Laurier University, Canada
P26F
P27
P28
P29
P30
P31
P32F
Ribosomal lipopeptides defined by distinct fatty N-acylation Florian Hubrich ETH Zurich, Switzerland
P33
Integrating culture dependent and independent methods to cultivate and isolate unculturable acidobacteria from Antarctic permafrost soils Lobna Hudifa Warwick University, UK
P34
Structural studies of deoxypodophyllotoxin synthase (DPS), a C-C bond forming enzyme Zoe Ingold University of York, UK Pyochelin biotransformation shapes bacterial competition Christian Jenul University of Colorado, USA Towards the discovery of antimicrobial natural products made by Trichoderma spp. and study of their biosynthesis Sophie Jin University of Warwick, UK Bioinformatics tool for genome mining of gene clusters encoding structurally interesting metabolites Stanislav Kadlcik Institute of Microbiology of the Czech Academy of Sciences, Czech Republic NRPS design guided by adenylation promiscuity Hajo Kries Leibniz Institute for Natural Product Research and Infection Biology (HKI), Germany Mutasynthesis of halogenated aurachins in escherichia coli Sebastian Kruth TU Dortmund University, Germany Expansion of the domain-spanning borosin family of RiPP natural products Aileen Lee University of Minnesota, USA Linking natural product synthesis to cell growth with gcFront Laurence Legon University of Warwick, UK Identification and structure of glycerol dibiphytanyl glycerol tetraether synthase Cody Lloyd The Pennsylvania State University, USA
P35
P36
P37
P38F
P39
P40
P41F
P42F
P43
Development of myoglobin-based catalyst for reactions with organic radicals Andriy Lubskyy Adolphe Merkle Institute, Switzerland Unique enzyme chemistry in the biosynthesis of a cyanobacteria neurotoxin April Lukowski University of California at San Diego, USA
P44F
P45
Elucidation of the crystal structure of the clorothricin decalin synthase of Streptomyces antibioticus
Monserrat Manzo Ruiz University of Bristol, UK
P46
Study of novel UV absorbing compounds in Cyanobacteria and characterisation of their photochemical properties Paula Martin De Prado University of Warwick, UK
P47
Discovery of origamins: extensively modified ribosomal peptides with up to 43 post-translational modifications
Christoph Martin Meier ETH Zurich, Switzerland
P48
Unraveling diterpenoid alkaloid biosynthesis in Aconitum Lana Mutabdzija Institute of Organic Chemistry and Biochemistry of the CAS, Czech Republic Biosynthesis and diversification of polyene antifungals with improved properties using tailoring enzymes Saadia Nasr Mirza University of Manchester, UK
P49
P50
Discovery of a novel cyclic lipopeptide and its biosynthetic gene cluster from a BAC library of Kutzneria sp.
Francisco Javier Ortiz-López Fundacion MEDINA, Spain
P51
Identification, cloning and heterologous expression of the gene cluster encoding globomycin biosynthesis Daniel Oves-Costales Fundacion MEDINA, Spain
P52
The role of thioesterase domain catalysed hydrolysis in preventing chain extension in polyketide synthases Fang Pang University of Warwick, UK
P53
Investigating docking domains in biosynthetic systems Munro Passmore University of Warwick, UK
P54
Investigation of tailoring steps in antibiotic peptide biosynthesis Jessica Peate King’s College London, UK Programming nonribosomal peptide synthetases with DNA templates Huiyun Peng Leibniz Institute for Natural Product Research and Infection Biology, Germany Genetics independent readout for high throughput elicitor screens using flow injection DAD-MS Ignacio Pérez-Victoria Fundación MEDINA, Spain Probing diverse β-branching mechanisms in polyketide biosynthesis with in vitro state-of-the-art NMR assays Annabel Phillips University of Bristol, UK Mechanistic studies of ureido bond formation by the NRPS involved in anabaenaopeptin biosynthesis Benjamin Philmus Oregon State University, USA Structural analysis of ether bridge forming dioxygenases in nargenicin macrolide biosynthesis Sacha Pidot The University of Melbourne, Australia Assessing the engineering potential of polymyxin antibiotics via heterologous expression in Bacillus subtilis Hanne Put KU Leuven - VIB, Belgium
P55
P56F
P57F
P58
P59F
P60
P61
Daphniphyllum alkaloids biosynthesis Barbara Radzikowska University of York, UK
P62
Exploring the chemical diversity of bartolosides – a group of cyanobacterial chlorinated dialkylresorcinols João Reis ICBAS, Portugal In situ modification of FR900359 biosynthesis in Chromobacterium vaccinii MWU205 René Richarz University of Bonn, Germany Site-specific, bioorthogonal protein labeling using endogenous β-amino acid dienophiles derived from natural product biosynthesis Daniel Richter ETH Zurich, Switzerland New drugs, old scaffold: new antimicrobials against bacterial folate biosynthesis Lynden Rooms University of Bristol, UK Exploring epoxyketone synthases and their biosynthetic potential Marlene Rothe University of Warwick, UK
P63
P64
P65
P66
P67
Identification of a novel cacaoidin derivative obtained by the heterologuos expression of the cao biosynthetic gene cluster
Marina Sánchez-Hidalgo Fundación MEDINA, Spain
P68F
Structural expansion and assembly line promiscuity in the biosynthesis of actinochelins, a widespread family of siderophores from Actinobacteria.
Javier Santos-Aberturas John Innes Centre, UK
P69
Biosynthetic studies on tropolone maleic acid anhydride conjugates from Hypoxylon lienhwacheense Katharina Schmidt Leibniz Universität Hannover, Germany Broad utilization of α-keto-β-amino acid-installing peptide chemistry in the microbial world Thomas Scott ETH Zürich, Switzerland Protein-ligand interactions: a tool for discovery of bioactive natural products from environmental mixtures Ludek Sehnal Masaryk University, Czech Republic
P70F
P71
P72F
The structure and function of cyanophycin synthetase Itai Sharon McGill University, Canada
P73
Convergent evolution of stereodivergent p-menthane gene clusters in Lamiaceae Samuel Smit University of York, UK Reconstitution of a split C-methylating module from the gladiolin trans- AT polyketide synthase Helen Smith University of Warwick, UK Heterologous expression confirms that the cyanobacterial mic gene cluster is responsible for the biosynthesis of the protease inhibitors microginins Diana Sousa University of Porto and Interdisciplinary Centre of Marine and Environmental Research, Portugal Developing a polyketide synthase module-centered multi-enzyme cascade for chemoenzymatic synthesis of antifungal polyketides Jörg Stang University of Bayreuth, Germany
P74F
P75
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P77
Bio-Production of adipic acid from lignin aromatics and terephthalic acid in engineered escherichia coli Jack Suitor University of Edinburgh, UK Discovery and biosynthetic origin of cyclopropanol-substituted toxins in human-pathogenic bacteria Felix Trottmann Leibniz Institute for Natural Product Research and Infection Biology, Germany
P78
P79
Elucidating the biosynthetic pathway of valclavam Katsiaryna Usachova John Innes Centre, UK Probing the structure-activity relationship of enacyloxins Daniel Van University of Warwick, UK
P80
P81F
Promiscuity of sesquiterpene cyclases using cyclopropylidene farnesyl pyrophosphate Catherine Victoria Leibniz Universität Hannover, Germany Characterizing the oximidine biosynthetic assembly line for the engineering of novel anticancer agents Eveline Vriens KU Leuven - VIB Center for Microbiology, Belgium Biosynthesis of menisporopsin A, a fungal macrocyclic polylactone Pakorn Wattana-Amorn Kasetsart University, Thailand Studies on pleurotin-producing fungi and heterologous hosts for elucidation of biosynthesis Jack Weaver University of Warwick, UK Development of a second-generation 13C-NMR assay to study β-branch formation in the kalimantacin antibiotics. Angus Weir KU Leuven - VIB, Belgium
P82F
P83
P84
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P86
Microbial H2 for biocompatible metabolite hydrogenation in vivo Mirren White University of Edinburgh, UK Engineered biosynthesis of indole alkaloids in Myxococcus xanthus Lea Winand TU Dortmund University, Germany Characterising the function and structure of a unique trans- acyltransferase enzyme from a modular polyketide synthase Fraser Windsor University of Western Australia, Australia The structure and function of the alpha-hydroxylation module of the mupirocin polyketide synthase. Ash Winter University of Bristol, UK Heterologous expression and engineering of Mycosporine-like amino- acid (MAA) biosynthetic gene clusters in Streptomyces hosts Sopida Wongwas University of Warwick, UK Securing securinine: the biosynthesis of a unique tetracyclic alkaloid Catharine Wood University of York, UK Expanding the CRISPR activation toolbox for secondary metabolite discovery in filamentous fungi Clara Woodcraft University of Western Australia, Australia Reprogram fungal modular NRPSs for production of “designer” alkaloids Coco Xie University of Western Australia, Australia Scleric acid biosynthesis studies and semisynthetic derivatives Jingfan Zhang University of Warwick, UK
P87F
P88
P89
P90
P91
P92
P93
P94
P95
Unusual chain initiation mechanism in gladiolin and gladiostatin biosynthesis Yu Zhang University of Warwick, UK Parallel gene editing of the cepacin biosynthetic gene cluster in yeast identifies key branch point in cepacin A and collimonins C/D biosynthesis Jinlian Zhao University of Warwick, UK Investigating the pharmaceutical potential of brown rot basidiomycetes Suhad Al-Salihi University of Technology, Iraq Global genome mining reveals multiprenylated cyclodipeptides with enhanced neuroprotective activity Jessie James Limlingan Malit The Hong Kong University of Science and Technology, Hong Kong NAD acting as a building block in natural product biosynthesis Lena Barra Universität Konstanz, Germany
P96F
P97
P98F
P99
Genome mining for unknown unknowns in fungi Yi Tang University of California, USA
Genome mining is a promising approach to discover new natural products from sequenced microbes. Current genome mining approaches rely on the presence of well-studied core enzymes such as PKS and NRPS to identify lead biosynthetic gene clusters. Here we present our discovery of "unknown unknown" natural products from fungi. These are natural products derived from biosynthetic pathways that do not contain a previously known core enzyme. As a result, the biosynthetic gene cluster do not provide clues to the structure of the natural product. We will present two examples of identifying new compounds from such pathways in fungi. In both examples, we characterized the new scaffold-forming enzymes, and use these as leads to mine additional pathways. Our results highlight potential to new natural products when we prioritize "unknown unknown" clusters.
K01
© The Author(s), 2022
Structural studies of transient and higher-order interactions in polyketide synthases Yves U. Tittes 1 , Hugo Muñoz-Hernandez 1 , Jamie R. Alley 2 , Dominik A. Herbst 1 , Callie R. Huitt-Roehl 2 , Jacob M. Kravetz 2 , Philip A. Storm 2 , Craig A. Townsend 2 and Timm Maier 1 1 Biozentrum, University of Basel, Switzerland, 2 Department of Chemistry, Johns Hopkins University, USA The multi-step biosynthesis of polyketides by polyketide synthases (PKSs) relies on the productive interplay of enzymes or enzymatic domains, often embedded as functional modules into large multifunctional proteins, with carrier proteins for substrate shuttling. Substantial progress has been made in understanding the architecture of individual domains and modules in PKSs, but studying transient interactions for substrate transfer in the context of multidomain proteins and visualising assemblies of PKS modules remain substantial challenges. We have analysed transient states of substrate transfer in an iterative non-reducing PKS based on specific crosslinking stabilisation of carrier protein interactions and cryo electron microscopy (cryoEM). We obtain snapshots of functional states that reveal intrinsic and state-specific interactions and dynamics within iterative non-reducing PKS. A single functional core is sufficient for polyketide biosynthesis by iterative PKS, but the most versatile families of modular PKS utilise assembly lines of connected functional modules. The organisation of modular PKS beyond a single module provides the framework for directed substrate transfer between modules, but experimental structural studies of higher-order PKS assemblies have been hindered by their considerable intrinsic flexibility. We have studied a modular PKS bimodule core fragment containing two substrate elongating condensing domains. CryoEM analysis of the bimodule core at multiple levels provides structural insights from high-resolution analysis of individual condensing domains to the arrangement of successive modules at intermediate resolution. Overall, our analyses emphasise the relevance of transient and dynamic interactions between domains in PKS and provide important information for mechanistic studies of PKS in vitro as well as for resolving the structural organisation of polyketide biosynthesis in vivo .
K02
© The Author(s), 2022
Structures and functions of nonribosomal and non-nonribosomal peptide synthetases Martin Schmeing McGill University, Canada Nonribosomal peptide synthetases (NRPSs) are true macromolecular machines, having modular assembly-line logic, a complex catalytic cycle, moving parts and many active sites. We have performed structural and functional analyses of components of the NRPS systems responsible for the syntheses of the antibiotic gramicidin, the anti-algae bacillamide, the anti-cancer agent valinomycin and the novel compound maxibactin. Results from these studies provide insight into the superdomain and supermodular architecture, conformational changes and mechanisms of tailoring that NRPSs use to synthesize their important bio-active products. In addition, we have performed structural and functional characterization of the non-NRPS enzyme cyanophycin synthetase. Cyanophycin is a natural biopolymer consisting of a chain of poly-L-Asp residues with L-Arg residues attached to the carboxylate side chains by isopeptide bonds. It is used in a wide range of bacteria for cellular nitrogen storage. Our studies reveal how activities from three domains combine to allow elegant processive polymerization of long chains of cyanophycin.
K03
© The Author(s), 2022
Repurposed biocatalysts for the assembly of antibiotics and toxins Christian Hertweck Leibniz Institute for Natural Product Research and Infection Biology (HKI), Germany Genome mining has greatly facilitated the identification of talented producer strains in neglected phyla. Yet, many non-canonical assembly lines evade bioinformatics predictions. When studying the biosynthesis of various structurally unique toxins and antibiotics in Gram-negative and anaerobic bacteria, we have come across unusual transformations involving biocatalysts that likely emerged from central metabolism and RNA modification. Beyond this intriguing evolutionary aspect, knowledge on these enzymes may be used for the development of novel biocatalysts and/or therapeutic approaches. Recent progress in studying biosynthetic pathways in unconventional producer strains at the genetic, biochemical and structural levels is presented.
K04
© The Author(s), 2022
New insights into cobalamin-dependent methyltransferase reactions Squire Booker Penn State University, USA Biological methylation underpins myriad cellular processes through the modification of proteins, lipids, nucleic acids, heavy metals, and a variety of small organic molecules. In the vast majority of these reactions, the appended methyl group derives from S -adenosylmethionine (SAM) and is attached most often to nitrogen and oxygen nucleophiles through a polar S N 2 mechanism, although carbon, sulfur, and a variety of other nucleophilic atoms also receive SAM-derived methyl groups. Recently, it has become apparent that SAM is used to methylate non-reactive carbon and phosphorus atoms by mechanisms involving radical intermediates. To date, these reactions are catalyzed exclusively by radical SAM enzymes, a superfamily of enzymes that use an iron-sulfur (Fe-S) cluster to catalyze a reductive cleavage of SAM to methionine and the potent oxidant 5’-deoxyadenosin 5’-radical (5’-dA•). There are at least five subclasses of radical SAM methylases. Class B methylases represent the largest subclass, and use cobalamin to methylate both sp 2 - and sp 3 -hybridized carbon centers or phosphinate phosphorus centers during the biosynthesis of numerous biomolecules, including natural products with antibiotic and anticancer activities. This lecture will focus on two Class B radical SAM methylases involved in the biosynthesis of antibacterial natural products that act by completely distinct mechanisms.
K05
© The Author(s), 2022
Combining organic synthesis and synthetic biology to explore and exploit polyketide biosynthesis Chris Willis University of Bristol, UK Polyketide-derived natural products isolated from microorganisms exhibit a range of important biological activities making them attractive leads for the development of therapeutics and agrochemicals. They are assembled in the host organism via sophisticated multiple enzyme architectures – polyketide synthases. Our overall aim is to fully understand how polyketides are produced to enable rational engineering of the complex biosynthetic machinery to deliver novel bioactive compounds cleanly and efficiently in scalable amounts. This lecture will focus on the combination of synthetic biology and organic synthesis to investigate polyketide biosynthesis thus enabling the generation of new bioactive targets and biocatalysts of potential widespread value. Examples will be taken from our recent work and will show case the value of a combined selective carbon-13 labelling/ NMR strategy to probe enzyme-catalysed transformations in situ. References 1. J. Byrne, N.R. Lees, L.-C Han, M. van der Kamp, A.J. Mulholland, J.E.M. Stach, C.L. Willis and P.R. Race, The catalytic mechanism of a natural Diels-Alderase revealed in molecular detail J. Am. Chem. Soc . 2016 , 138 , 6095. 2. L. Wang, A.E. Parnell, C. Williams, N.A. Baker, M.R. Challand, M. van der Kamp, T.J. Simpson, P. R. Race, M..P. Crump and C. L. Willis, A Rieske oxygenase/epoxide hydrolase-catalysed reaction cascade creates oxygen heterocycles in mupirocin biosynthesis Nature Catalysis , 2018 , 1 , 968. 3. N.R. Lees, L.C Han, M.J. Byrne, J.A. Davies, A.E. Parnell, P.E.J. Moreland, J.E.M. Stach, M.W. van der Kamp, C.L. Willis and P.R. Race, An esterase-like lyase catalyzes acetate elimination in spirotetronate/ spirotetramate biosynthesis Angew. Chem. Int. Ed. 2019 , 58 , 2305. 4. L. Wang, Z. Song, P.R. Race, J. Spencer, T.J. Simpson, M.P. Crump and C.L. Willis, Mixing and matching genes of marine and terrestrial origin in the biosynthesis of the mupirocin antibiotics, Chem Sci. , 2020 , 11 , 5221-5226.
K06
© The Author(s), 2022
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