The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform
Takuji Nakashima - One of the best experts on this subject based on the ideXlab platform.
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Pyrizomicin A and B: structure and bioactivity of new thiazolyl pyridines from Lechevalieria aerocolonigenes K10-0216
The Journal of Antibiotics, 2018Co-Authors: Tōru Kimura, Yōko Takahashi, Masato Iwatsuki, Satoshi Ōmura, Yuki Inahashi, Hirotaka Matsuo, Takuya Suga, Kazuro Shiomi, Takuji NakashimaAbstract:Two new antibiotics, designated pyrizomicin A and B, were isolated from the cultured broth of a rare actinomycete strain, Lechevalieria aerocolonigenes K10-0216, by silica gel and HPLC purification. The chemical structures of pyrizomicin A and B were elucidated as new thiazolyl pyridine compounds by nuclear magnetic resonance and mass spectrometry. Pyrizomicin A and B both showed antimicrobial activity.
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Actinomycetes, an Inexhaustible Source of Naturally Occurring Antibiotics.
The Journal of antibiotics, 2018Co-Authors: Yōko Takahashi, Takuji NakashimaAbstract:Global public health faces a desperate situation, due to the lack of effective antibiotics. Coordinated steps need to be taken, worldwide, to rectify this situation and protect the advances in modern medicine made over the last 100 years. Work at Japan’s Kitasato Institute has been in the vanguard of many such advances, and work is being proactively tailored to promote the discovery of urgently needed antimicrobials. Efforts are being concentrated on actinomycetes, the proven source of most modern antibiotics. We devised a novel physicochemical screening mechanism, whereby simple physico-chemical properties, in conjunction with related detection methods, such as LC/MS, LC/UV, and polarity, could be used to identify or predict new compounds in a culture broth, simply by comparing results with existing databases. New compounds are isolated, purified, and their structure determined before being tested for any bioactivity. We used lyophilized actinomycete strains from the Kitasato Microbial Library, most more than 35 years old, and found 330 strains were producers of useful bioactive substances. We also tested organisms found in fresh samples collected in the complex environments from around plant roots, as well as from sediments of mangrove forests and oceans, resulting in the discovery of 36 novel compounds from 11 actinomycete strains. A compound, designated iminimycin, containing an iminium ion in the structure was discovered from the culture broth of Streptomyces griseus OS-3601, which had been stored for a long time as a streptomycin-producing strain. This represented the first iminium ion discovery in actinomycetes. Compounds with a cyclopentadecane skeleton containing 5,6-dihydro-4-hydroxyl-2-pyrone ring and tetrahydrofuran ring, designated mangromicins, were isolated from the culture broth of Lechevalieria aerocolonigenes K10-0216 obtained from sediment in a mangrove forest. These structures are extremely unique among natural compounds. From the same culture broth, new steroid compounds, named K10-0216 KA and KB, and other new compounds having a thiazole and a pyridine ring, named pyrizomicin A and B, were discovered. New substances can be found from actinomycetes that have been exhaustively studied. Novel compounds with different skeletons can be found from a single broth of one strain. The sought after new antibiotics will arise from continued exploitation of the actinomycetes, especially rare actinomycetes. Work on new organisms and samples should be augmented by re-examination of known actinomycetes already in storage. New research should also be carried out on the manipulation of culture media, thereby stimulating actinomycete strains to produce novel chemicals. The establishment of wide-ranging international research collaborations will facilitate and expedite the efficient and timely discovery and provision of bioactive compounds to help maintain and promote advances in global public health.
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New steroidal compounds from an actinomycete strain, Lechevalieria aerocolonigenes K10-0216.
The Journal of antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Kenzaburo Yamaji, Noriko Sato, Satoshi ŌmuraAbstract:New steroidal compounds from an actinomycete strain, Lechevalieria aerocolonigenes K10-0216
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Mangromicin C, a new analog of mangromicin
The Journal of antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Noriko Sato, Satoshi ŌmuraAbstract:Mangromicin analogs were discovered in a cultured broth of a rare actinomycete, Lechevalieria aerocolonigenes K10-0216.1,2 The mangromicin analogs showed antitrypanosomal and reactive oxygen species (ROS) scavenging bioactivities. Mangromicin analogs have unique structures, including common partial structures, notably a cyclopentadecane skeleton with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. In a previous report, we described eight new mangromicin analogs, which possessed anti-oxidative properties. At that time, we discovered mangromicin C (1) but were unable to determine its structure, which was clearly different from all the other analogs. We have now found that 1 has a structure which includes a tetrahydropyran ring (Figure 1). In this paper, we report the fermentation, isolation, structural elucidation and biological activity of 1.
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mangromicins six new anti oxidative agents isolated from a culture broth of the actinomycete Lechevalieria aerocolonigenes k10 0216
The Journal of Antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Satoshi ōmuraAbstract:We have been continually searching for novel chemical compounds from culture broths of various actinomycetes using a physicochemical screening system. During the course of this program, we have previously reported the discovery of two new natural products, designated mangromicins A and B, discovered in a broth of a rare actinomycete strain, Lechevalieria aerocolonigenes K10-0216. Mangromicins have a unique and rare structure, a cyclopentadecane skeleton with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. New mangromicin analogs were isolated by using an improved production medium. As a consequence, six analogs, together with mangromicins A and B, were isolated from a cultured broth of L. aerocolonigenes K10-0216. We named them mangromicins D, E, F, G, H and I. All mangromicins showed radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and nitric oxide generated from LPS-stimulated RAW264.7 cells, a murine macrophage cell line. Among the analogs, mangromicins A and I showed the most potent DPPH radical scavenging activity and nitric oxide scavenging activity, respectively.
Yōko Takahashi - One of the best experts on this subject based on the ideXlab platform.
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Pyrizomicin A and B: structure and bioactivity of new thiazolyl pyridines from Lechevalieria aerocolonigenes K10-0216
The Journal of Antibiotics, 2018Co-Authors: Tōru Kimura, Yōko Takahashi, Masato Iwatsuki, Satoshi Ōmura, Yuki Inahashi, Hirotaka Matsuo, Takuya Suga, Kazuro Shiomi, Takuji NakashimaAbstract:Two new antibiotics, designated pyrizomicin A and B, were isolated from the cultured broth of a rare actinomycete strain, Lechevalieria aerocolonigenes K10-0216, by silica gel and HPLC purification. The chemical structures of pyrizomicin A and B were elucidated as new thiazolyl pyridine compounds by nuclear magnetic resonance and mass spectrometry. Pyrizomicin A and B both showed antimicrobial activity.
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Actinomycetes, an Inexhaustible Source of Naturally Occurring Antibiotics.
The Journal of antibiotics, 2018Co-Authors: Yōko Takahashi, Takuji NakashimaAbstract:Global public health faces a desperate situation, due to the lack of effective antibiotics. Coordinated steps need to be taken, worldwide, to rectify this situation and protect the advances in modern medicine made over the last 100 years. Work at Japan’s Kitasato Institute has been in the vanguard of many such advances, and work is being proactively tailored to promote the discovery of urgently needed antimicrobials. Efforts are being concentrated on actinomycetes, the proven source of most modern antibiotics. We devised a novel physicochemical screening mechanism, whereby simple physico-chemical properties, in conjunction with related detection methods, such as LC/MS, LC/UV, and polarity, could be used to identify or predict new compounds in a culture broth, simply by comparing results with existing databases. New compounds are isolated, purified, and their structure determined before being tested for any bioactivity. We used lyophilized actinomycete strains from the Kitasato Microbial Library, most more than 35 years old, and found 330 strains were producers of useful bioactive substances. We also tested organisms found in fresh samples collected in the complex environments from around plant roots, as well as from sediments of mangrove forests and oceans, resulting in the discovery of 36 novel compounds from 11 actinomycete strains. A compound, designated iminimycin, containing an iminium ion in the structure was discovered from the culture broth of Streptomyces griseus OS-3601, which had been stored for a long time as a streptomycin-producing strain. This represented the first iminium ion discovery in actinomycetes. Compounds with a cyclopentadecane skeleton containing 5,6-dihydro-4-hydroxyl-2-pyrone ring and tetrahydrofuran ring, designated mangromicins, were isolated from the culture broth of Lechevalieria aerocolonigenes K10-0216 obtained from sediment in a mangrove forest. These structures are extremely unique among natural compounds. From the same culture broth, new steroid compounds, named K10-0216 KA and KB, and other new compounds having a thiazole and a pyridine ring, named pyrizomicin A and B, were discovered. New substances can be found from actinomycetes that have been exhaustively studied. Novel compounds with different skeletons can be found from a single broth of one strain. The sought after new antibiotics will arise from continued exploitation of the actinomycetes, especially rare actinomycetes. Work on new organisms and samples should be augmented by re-examination of known actinomycetes already in storage. New research should also be carried out on the manipulation of culture media, thereby stimulating actinomycete strains to produce novel chemicals. The establishment of wide-ranging international research collaborations will facilitate and expedite the efficient and timely discovery and provision of bioactive compounds to help maintain and promote advances in global public health.
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New steroidal compounds from an actinomycete strain, Lechevalieria aerocolonigenes K10-0216.
The Journal of antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Kenzaburo Yamaji, Noriko Sato, Satoshi ŌmuraAbstract:New steroidal compounds from an actinomycete strain, Lechevalieria aerocolonigenes K10-0216
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Mangromicin C, a new analog of mangromicin
The Journal of antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Noriko Sato, Satoshi ŌmuraAbstract:Mangromicin analogs were discovered in a cultured broth of a rare actinomycete, Lechevalieria aerocolonigenes K10-0216.1,2 The mangromicin analogs showed antitrypanosomal and reactive oxygen species (ROS) scavenging bioactivities. Mangromicin analogs have unique structures, including common partial structures, notably a cyclopentadecane skeleton with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. In a previous report, we described eight new mangromicin analogs, which possessed anti-oxidative properties. At that time, we discovered mangromicin C (1) but were unable to determine its structure, which was clearly different from all the other analogs. We have now found that 1 has a structure which includes a tetrahydropyran ring (Figure 1). In this paper, we report the fermentation, isolation, structural elucidation and biological activity of 1.
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mangromicins six new anti oxidative agents isolated from a culture broth of the actinomycete Lechevalieria aerocolonigenes k10 0216
The Journal of Antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Satoshi ōmuraAbstract:We have been continually searching for novel chemical compounds from culture broths of various actinomycetes using a physicochemical screening system. During the course of this program, we have previously reported the discovery of two new natural products, designated mangromicins A and B, discovered in a broth of a rare actinomycete strain, Lechevalieria aerocolonigenes K10-0216. Mangromicins have a unique and rare structure, a cyclopentadecane skeleton with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. New mangromicin analogs were isolated by using an improved production medium. As a consequence, six analogs, together with mangromicins A and B, were isolated from a cultured broth of L. aerocolonigenes K10-0216. We named them mangromicins D, E, F, G, H and I. All mangromicins showed radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and nitric oxide generated from LPS-stimulated RAW264.7 cells, a murine macrophage cell line. Among the analogs, mangromicins A and I showed the most potent DPPH radical scavenging activity and nitric oxide scavenging activity, respectively.
Masato Iwatsuki - One of the best experts on this subject based on the ideXlab platform.
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Pyrizomicin A and B: structure and bioactivity of new thiazolyl pyridines from Lechevalieria aerocolonigenes K10-0216
The Journal of Antibiotics, 2018Co-Authors: Tōru Kimura, Yōko Takahashi, Masato Iwatsuki, Satoshi Ōmura, Yuki Inahashi, Hirotaka Matsuo, Takuya Suga, Kazuro Shiomi, Takuji NakashimaAbstract:Two new antibiotics, designated pyrizomicin A and B, were isolated from the cultured broth of a rare actinomycete strain, Lechevalieria aerocolonigenes K10-0216, by silica gel and HPLC purification. The chemical structures of pyrizomicin A and B were elucidated as new thiazolyl pyridine compounds by nuclear magnetic resonance and mass spectrometry. Pyrizomicin A and B both showed antimicrobial activity.
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New steroidal compounds from an actinomycete strain, Lechevalieria aerocolonigenes K10-0216.
The Journal of antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Kenzaburo Yamaji, Noriko Sato, Satoshi ŌmuraAbstract:New steroidal compounds from an actinomycete strain, Lechevalieria aerocolonigenes K10-0216
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Mangromicin C, a new analog of mangromicin
The Journal of antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Noriko Sato, Satoshi ŌmuraAbstract:Mangromicin analogs were discovered in a cultured broth of a rare actinomycete, Lechevalieria aerocolonigenes K10-0216.1,2 The mangromicin analogs showed antitrypanosomal and reactive oxygen species (ROS) scavenging bioactivities. Mangromicin analogs have unique structures, including common partial structures, notably a cyclopentadecane skeleton with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. In a previous report, we described eight new mangromicin analogs, which possessed anti-oxidative properties. At that time, we discovered mangromicin C (1) but were unable to determine its structure, which was clearly different from all the other analogs. We have now found that 1 has a structure which includes a tetrahydropyran ring (Figure 1). In this paper, we report the fermentation, isolation, structural elucidation and biological activity of 1.
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mangromicins six new anti oxidative agents isolated from a culture broth of the actinomycete Lechevalieria aerocolonigenes k10 0216
The Journal of Antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Satoshi ōmuraAbstract:We have been continually searching for novel chemical compounds from culture broths of various actinomycetes using a physicochemical screening system. During the course of this program, we have previously reported the discovery of two new natural products, designated mangromicins A and B, discovered in a broth of a rare actinomycete strain, Lechevalieria aerocolonigenes K10-0216. Mangromicins have a unique and rare structure, a cyclopentadecane skeleton with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. New mangromicin analogs were isolated by using an improved production medium. As a consequence, six analogs, together with mangromicins A and B, were isolated from a cultured broth of L. aerocolonigenes K10-0216. We named them mangromicins D, E, F, G, H and I. All mangromicins showed radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and nitric oxide generated from LPS-stimulated RAW264.7 cells, a murine macrophage cell line. Among the analogs, mangromicins A and I showed the most potent DPPH radical scavenging activity and nitric oxide scavenging activity, respectively.
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Mangromicins, six new anti-oxidative agents isolated from a culture broth of the actinomycete, Lechevalieria aerocolonigenes K10-0216
The Journal of Antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Satoshi OmuraAbstract:Mangromicins, six new anti-oxidative agents isolated from a culture broth of the actinomycete, Lechevalieria aerocolonigenes K10-0216
Yoshiyuki Kamiya - One of the best experts on this subject based on the ideXlab platform.
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New steroidal compounds from an actinomycete strain, Lechevalieria aerocolonigenes K10-0216.
The Journal of antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Kenzaburo Yamaji, Noriko Sato, Satoshi ŌmuraAbstract:New steroidal compounds from an actinomycete strain, Lechevalieria aerocolonigenes K10-0216
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Mangromicin C, a new analog of mangromicin
The Journal of antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Noriko Sato, Satoshi ŌmuraAbstract:Mangromicin analogs were discovered in a cultured broth of a rare actinomycete, Lechevalieria aerocolonigenes K10-0216.1,2 The mangromicin analogs showed antitrypanosomal and reactive oxygen species (ROS) scavenging bioactivities. Mangromicin analogs have unique structures, including common partial structures, notably a cyclopentadecane skeleton with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. In a previous report, we described eight new mangromicin analogs, which possessed anti-oxidative properties. At that time, we discovered mangromicin C (1) but were unable to determine its structure, which was clearly different from all the other analogs. We have now found that 1 has a structure which includes a tetrahydropyran ring (Figure 1). In this paper, we report the fermentation, isolation, structural elucidation and biological activity of 1.
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mangromicins six new anti oxidative agents isolated from a culture broth of the actinomycete Lechevalieria aerocolonigenes k10 0216
The Journal of Antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Satoshi ōmuraAbstract:We have been continually searching for novel chemical compounds from culture broths of various actinomycetes using a physicochemical screening system. During the course of this program, we have previously reported the discovery of two new natural products, designated mangromicins A and B, discovered in a broth of a rare actinomycete strain, Lechevalieria aerocolonigenes K10-0216. Mangromicins have a unique and rare structure, a cyclopentadecane skeleton with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. New mangromicin analogs were isolated by using an improved production medium. As a consequence, six analogs, together with mangromicins A and B, were isolated from a cultured broth of L. aerocolonigenes K10-0216. We named them mangromicins D, E, F, G, H and I. All mangromicins showed radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and nitric oxide generated from LPS-stimulated RAW264.7 cells, a murine macrophage cell line. Among the analogs, mangromicins A and I showed the most potent DPPH radical scavenging activity and nitric oxide scavenging activity, respectively.
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Mangromicins, six new anti-oxidative agents isolated from a culture broth of the actinomycete, Lechevalieria aerocolonigenes K10-0216
The Journal of Antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Yōko Takahashi, Masato Iwatsuki, Satoshi OmuraAbstract:Mangromicins, six new anti-oxidative agents isolated from a culture broth of the actinomycete, Lechevalieria aerocolonigenes K10-0216
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Mangromicins A and B: structure and antitrypanosomal activity of two new cyclopentadecane compounds from Lechevalieria aerocolonigenes K10-0216
The Journal of Antibiotics, 2014Co-Authors: Takuji Nakashima, Yoshiyuki Kamiya, Masato Iwatsuki, Kazuro Shiomi, Junya Ochiai, Kenichiro Nagai, Atsuko Matsumoto, Aki Ishiyama, Kazuhiko Otoguro, Yōko TakahashiAbstract:Two new cyclopentadecane antibiotics, named mangromicins A and B, were separated out from the culture broth of Lechevalieria aerocolonigenes K10-0216 by Diaion HP-20, silica gel and ODS column chromatography, and were finally purified by HPLC. The chemical structures of the two novel compounds were elucidated by instrumental analyses, including various NMR, MS and X-ray crystallography. Mangromicins A and B consist of cyclopentadecane skeletons with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. Mangromicins A and B showed in vitro antitrypanosomal activity with IC_50 values of 2.4 and 43.4 μg ml^−1, respectively. The IC_50 values of both compounds were lower than those of cytotoxicity against MRC-5 human fetal lung fibroblast cells.
David H. Sherman - One of the best experts on this subject based on the ideXlab platform.
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Molecular Analysis of the Rebeccamycin l-Amino Acid Oxidase from Lechevalieria aerocolonigenes ATCC 39243
Journal of bacteriology, 2005Co-Authors: Tomoyasu Nishizawa, Courtney C. Aldrich, David H. ShermanAbstract:Rebeccamycin, a member of the tryptophan-derived indolocarbazole family, is produced by Lechevalieria aerocolonigenes ATCC 39243. The biosynthetic pathway that specifies biosynthesis of this important metabolite is comprised of 11 genes spanning 18 kb of DNA. A presumed early enzyme involved in elaboration of the rebeccamycin aglycone is encoded by rebO, located at the left-hand region of the reb gene cluster. The deduced protein product, RebO (51.9 kDa), is an l-amino acid oxidase (l-AAO) that has 27% identity to an l-AAO from Scomber japonicus (animal, mackerel) and is a member of the family of FAD-dependent oxidase enzymes. In order to study the biochemical properties of this key enzyme, the rebO gene was overexpressed and purified from Escherichia coli. Biochemical characterization showed that RebO is dimeric, with a molecular mass of approximately 101 kDa. Further analysis revealed that the enzyme contains a noncovalently bound FAD cofactor and is reoxidized at the expense of molecular oxygen by producing one molecule of hydrogen peroxide. Based on kinetic studies, RebO shows significant preference for 7-chloro-l-tryptophan, suggesting its likely role as the natural early pathway substrate. Furthermore, the native RebO enzyme has evident, albeit limited, flexibility as shown by bioconversion studies with unnatural substrates. This work provides the first analysis of a structural enzyme involved in construction of this important class of indolocarbazole natural products.