Article
Chemistry, Multidisciplinary
Ashley J. Winter, Matthew T. Rowe, Angus N. M. Weir, Nahida Akter, Sbusisiwe Z. Mbatha, Paul D. Walker, Christopher Williams, Zhongshu Song, Paul R. Race, Christine L. Willis, Matthew P. Crump
Summary: In this study, the remaining steps of 9HN biosynthesis were investigated using NMR spectroscopy, mass spectrometry, chemical probes, and in vitro assays. The results reveal a complex interplay between multiple acyl carrier proteins and a novel KS-AT didomain.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Nikolai A. Loehr, Frederic Eisen, Wiebke Thiele, Lukas Platz, Jonas Motter, Wolfgang Huettel, Markus Gressler, Michael Mueller, Dirk Hoffmeister
Summary: This study describes an unprecedented class of non-reducing polyketide synthases (NR-PKS) that can synthesize octaketide pigments. The researchers identified CoPKS1 and CoPKS4 of the mushroom genus Cortinarius as new atrochrysone carboxylic acid synthases. These findings illustrate how the biosynthesis of bioactive metabolites evolved independently in different groups of organisms.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Jeffrey T. Mindrebo, Aochiu Chen, Woojoo E. Kim, Rebecca N. Re, Tony D. Davis, Joseph P. Noel, Michael D. Burkart
Summary: The study focuses on the mechanism of ketosynthases, demonstrating the importance of interactions between active site loops and acyl carrier proteins in catalysis. It also provides evidence for the role of gating in the overall KS condensation reaction and explores the catalytic importance of these loops through mutagenesis and investigation of chimeric FabF constructs. These findings contribute to a better understanding of the KS mechanism and can inform future engineering efforts in fatty acid synthases and related polyketide synthases.
Review
Biochemistry & Molecular Biology
Martin Grininger
Summary: Modular polyketide synthases (PKSs) are highly organized enzymes that run catalytic reactions over multiple steps. These enzymes form complex multienzyme complexes and produce complex polyketide products. Recent structural insights have provided valuable information about the orchestration of catalytic events within PKSs, leading to new possibilities in PKS engineering.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Munro Passmore, Angelo Gallo, Jozef R. Lewandowski, Matthew Jenner
Summary: This study reveals specific interactions between ACP and KR domains from trans-AT PKSs, indicating highly optimized interaction interfaces driven by evolutionary processes. The results provide valuable rules for future engineering efforts of biosynthetic assembly lines.
Review
Biotechnology & Applied Microbiology
Chang Liu, Sijin Li
Summary: This review summarizes the progress made in the past 10 years in type III PKS-catalyzed natural product biosynthesis in microorganisms, with a focus on complete biosynthesis strategies and achievements.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Microbiology
Yu Yin, Rui Li, Wei-Ting Liang, Wen-Bin Zhang, Zhe Hu, Jin-Cheng Ma, Hai-Hong Wang
Summary: The study characterized the ACP genes in Ralstonia solanacearum and found that only AcpP1 is involved in the fatty acid synthesis pathway, while the other three ACP genes participate in different pathways. Disrupting the four ACP genes attenuated the bacterium's pathogenicity in the host plant.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Tobias Schwanemann, Maike Otto, Benedikt Wynands, Jan Marienhagen, Nick Wierckx
Summary: In this study, the researchers successfully enhanced the availability of malonyl-CoA in Pseudomonas taiwanensis VLB120, leading to increased production of polyketide compounds. The overexpression of acetyl-CoA carboxylase was found to play a key role in the production of polyketides, and its effectiveness depended on the strain-background and the impairment of downstream fatty acid synthesis.
METABOLIC ENGINEERING
(2023)
Article
Multidisciplinary Sciences
Hongjiao Zhang, Zixin Li, Shuang Zhou, Shu-Ming Li, Huomiao Ran, Zili Song, Tao Yu, Wen-Bing Yin
Summary: FnsA is a novel NRPS-PKS hybrid that is involved in the formation of naringenin. It activates both p-coumaric acid and p-hydroxybenzoic acid through its adenylation domain and uses malonyl-CoA molecules for elongation. Refactoring the biosynthetic pathway with fnsA in yeast provides an alternative approach for the production of flavonoids such as isorhamnetin and acacetin.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Anna-Kay R. West, Constance B. Bailey
Summary: The article discusses the interconnected biosynthesis between fatty acid synthases (FASs) and polyketide synthases (PKSs) in primary and secondary metabolism. Understanding the linkage between polyketide biosynthesis and fatty acid biosynthesis may lead to the discovery and production of novel drug leads from polyketide metabolites.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Shreya Kishore, Chaitan Khosla
Summary: By mining genomic data from the NCBI database, this study presents an updated catalogue of 8799 non-redundant assembly line polyketide synthase clusters across 4083 species, showing a threefold increase in the past 4 years. Furthermore, 95% of the clusters are 'orphan clusters' with no known chemical or biological characterization. These findings suggest that the diversity of assembly line PKSs remains largely unexplored and highlight the potential of genomics-driven approaches for natural product discovery.
Article
Chemistry, Organic
Siyar Kavakli, Gina L. C. Grammbitter, Helge B. Bode
Summary: This study revealed the role of StlB in the biosynthetic pathway of Isopropylstilbene (IPS) and demonstrated the cross-talk between enzymes from the bacterial fatty acid biosynthesis pathway and IPS synthesis pathway, resulting in the successful production of IPS in a heterologous host.
Article
Biochemistry & Molecular Biology
Fumitaka Kudo, Kosuke Kishikawa, Kazuma Tsuboi, Takafusa Kido, Takeo Usui, Junko Hashimoto, Kazuo Shin-ya, Akimasa Miyanaga, Tadashi Eguchi
Summary: In this study, the biosynthetic gene cluster for virustomycin A, an antibiotic produced by Streptomyces graminofaciens A-8890, was identified. The study also demonstrated the exchangeability of the acyltransferase domain between the PKSs involved in FD-891 biosynthesis and the Vsm PKSs. By exchanging the malonyltransferase domain in the loading module of the PKSs, a two-carbon-elongated analog 26-ethyl-FD-891 was successfully produced with potent cytotoxic activity.
Article
Biochemistry & Molecular Biology
Maybelle Kho Go, Tingting Zhu, Kevin Jie Han Lim, Yossa Dwi Hartono, Bo Xue, Hao Fan, Wen Shan Yew
Summary: We have discovered enzymes from the berberine bridge enzyme (BBE) superfamily that can catalyze the oxidative cyclization of the monoterpene moiety in cannabigerolic acid (CBGA) to form cannabielsoin (CBE). These previously uncharacterized enzymes were found in various organisms. Among 232 homologues chosen from the enzyme superfamily, four orthologues were identified to accept CBGA as a substrate and catalyze the biosynthesis of CBE. The recombinantly expressed and purified enzymes, obtained from Pichia pastoris, are the first reported heterologous expression of BBEs that can produce cannabinoids using CBGA as a substrate. This study presents a novel approach for the discovery and production of natural and unnatural cannabinoids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Russell J. Cox
Summary: Investigations over the past two decades have provided insights into the programming of fungal iterative highly-reducing polyketide synthases. Both in vitro and in vivo experiments have revealed the interaction between intrinsic and extrinsic selectivity of the catalytic domains in these systems. Structural biology has started to provide high resolution structures of hr-PKS that can be utilized for their engineering, although progress in this field is still at an early stage. However, there are significant opportunities to use the current understanding to reengineer these efficient systems for the production of important biologically active compounds through biotechnology.
NATURAL PRODUCT REPORTS
(2023)
Article
Biotechnology & Applied Microbiology
Shan Lu, Shinichi Nishimura, Masashi Ito, Taira Kato, Hideaki Kakeya
JOURNAL OF ANTIBIOTICS
(2017)
Article
Pharmacology & Pharmacy
Yoichi Sunagawa, Masafumi Funamoto, Shogo Sono, Kana Shimizu, Satoshi Shimizu, Mai Genpei, Yusuke Miyazaki, Yasufumi Katanasaka, Eriko Morimoto, Morio Ueno, Maki Komiyama, Hideaki Kakeya, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2018)
Article
Chemistry, Organic
Shan Lu, Shinichi Nishimura, Kei Takenaka, Masashi Ito, Taira Kato, Hideaki Kakeya
Article
Biochemistry & Molecular Biology
Kimberly Cornelio, Rafael Atillo Espiritu, Shinya Hanashima, Yasuto Todokoro, Raymond Malabed, Masanao Kinoshita, Nobuaki Matsumori, Michio Murata, Shinichi Nishimura, Hideaki Kakeya, Minoru Yoshida, Shigeki Matsunaga
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2019)
Article
Biochemistry & Molecular Biology
Nobuaki Takahashi, Kyohei Hayashi, Yusuke Nakagawa, Yutaka Furutani, Mariko Toguchi, Yumi Shiozaki-Sato, Masayuki Sudoh, Soichi Kojima, Hideaki Kakeya
BIOORGANIC & MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Organic
Yulu Jiang, Shan Lu, Go Hirai, Taira Kato, Hiroyasu Onaka, Hideaki Kakeya
TETRAHEDRON LETTERS
(2019)
Article
Multidisciplinary Sciences
Yutaka Furutani, Mariko Toguchi, Yumi Shiozaki-Sato, Xian-Yang Qin, Etsuko Ebisui, Shoko Higuchi, Masayuki Sudoh, Harukazu Suzuki, Nobuaki Takahashi, Koichi Watashi, Takaji Wakita, Hideaki Kakeya, Soichi Kojima
Article
Chemistry, Organic
Aya Yoshimura, Shinichi Nishimura, Takehiro Suzuki, Akira Hattori, Naoshi Dohmae, Taira Kato, Hideaki Kakeya
Article
Chemistry, Multidisciplinary
Ryosuke Sugiyama, Takahiro Nakatani, Shinichi Nishimura, Kei Takenaka, Taro Ozaki, Shumpei Asamizu, Hiroyasu Onaka, Hideaki Kakeya
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2019)
Article
Endocrinology & Metabolism
Masafumi Funamoto, Kana Shimizu, Yoichi Sunagawa, Yasufumi Katanasaka, Yusuke Miyazaki, Hideaki Kakeya, Hajime Yamakage, Noriko Satoh-Asahara, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
JOURNAL OF DIABETES RESEARCH
(2019)
Article
Oncology
Xuebing Li, Akira Hattori, Senye Takahashi, Yoko Goto, Hiroshi Harada, Hideaki Kakeya
Article
Cell Biology
Kosuke Baba, Sara Kuwada, Ayaka Nakao, Xuebing Li, Naoaki Okuda, Ai Nishida, Satoshi Mitsuda, Natsuki Fukuoka, Hideaki Kakeya, Takao Kataoka
HISTOCHEMISTRY AND CELL BIOLOGY
(2020)
Article
Chemistry, Multidisciplinary
Nobuaki Takahashi, Hideaki Hayashi, Viktors Poznaks, Hideaki Kakeya
CHEMICAL COMMUNICATIONS
(2019)
Article
Chemistry, Organic
Taro Ozaki, Ryosuke Sugiyama, Morito Shimomura, Shinichi Nishimura, Shumpei Asamizu, Yohei Katsuyama, Hideaki Kakeya, Hiroyasu Onaka
ORGANIC & BIOMOLECULAR CHEMISTRY
(2019)
Correction
Cardiac & Cardiovascular Systems
Mai Genpei, Yoichi Sunagawa, Masafumi Funamoto, Kana Shimizu, Yusuke Miyazaki, Yasufumi Katanasaka, Nobuaki Takahashi, Hideaki Kakeya, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
EUROPEAN CARDIOLOGY REVIEW
(2018)