AM-2282, a new alkaloid has been isolated from cultures of Streptomyces sp. AM-2282 by solvent extraction and silica gel chromatography. The compound exhibits a strong absorption maximum at 292 nm and shows antimicrobial activity against fungi and yeast. The LD50 of its hydrochloride (i.p. in mice) is 6.6 mg/kg. The molecular formula of AM-2282 has been determined as C28H26N4O3. The producing strain, AM-2282 was classified as a new species and the name, Streptomyces staurosporeus AWAYA, TAKAHASHI and OMURA, nov. sp. is proposed. We have previously reported on the isolation of new alkaloids such as pyrindicin1), NA-337A2), THE JOURNAL OF ANTIBIOTICS APR.

The secondary metabolites of higher plants include diverse chemicals, such as alkaloids, isoprenoids and phenolic compounds (phenylpropanoids and flavonoids). Although these compounds are widely used in human health and nutrition, at present they are mainly obtained by extraction from plants and extraction yields are low because most of these metabolites accumulate at low levels in plant cells. Recent advances in synthetic biology and metabolic engineering have enabled tailored production of plant secondary metabolites in microorganisms, but these methods often require the addition of expensive substrates. Here we develop an Escherichia coli fermentation system that yields plant alkaloids from simple carbon sources, using selected enzymes to construct a tailor-made biosynthetic pathway. In this system, engineered cells cultured in growth medium without additional substrates produce the plant benzylisoquinoline alkaloid, (S)-reticuline (yield, 46.0 mg l−1 culture medium). The fermentation platform described here offers opportunities for low-cost production of many diverse alkaloids.

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Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies. Fermentative opiate production in microbes has also been investigated, and complete biosynthesis of opiates from a simple carbon source has recently been accomplished in yeast. Here we demonstrate that Escherichia coli serves as an efficient, robust and flexible platform for total opiate synthesis. Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four engineered strains at yields of 2.1 mg l−1 from glycerol, corresponding to a 300-fold increase from recently developed yeast systems. This improvement is presumably due to strong activity of enzymes related to thebaine synthesis from (R)-reticuline in E. coli. Furthermore, by adding two genes to the thebaine production system, we demonstrate the biosynthesis of hydrocodone, a clinically important opioid. Improvements in opiate production in this E. coli system represent a major step towards the development of alternative opiate production systems.

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Herbimycin, a new antibiotic, was isolated from the fermentation broth of Streptomyces hygroscopicus strain No. AM-3672, a soil isolate. The molecular formula of herbimycin was determined to be C3oH42N209. Herbimycin was found to have potent herbicidal activity against most mono-and di-cotyledonous plants, especially against Cyperus microiria STEUD. However, Oryza sativa showed strong resistance to herbimycin.

Regio- and 1,2- cis-stereoselective chemical glycosylation of unprotected glycosyl acceptors has been in great demand for the efficient synthesis of natural glycosides. However, simultaneously regulating these selectivities has been a longstanding problem in synthetic organic chemistry. In nature, glycosyl transferases catalyze regioselective 1,2- cis-glycosylations via the Si mechanism, yet no useful chemical glycosylations based on this mechanism have been developed. In this paper, we report a highly regio- and 1,2- cis-stereoselective Si-type glycosylation of 1,2-anhydro donors and unprotected sugar acceptors using p-nitrophenylboronic acid (10e) as a catalyst in the presence of water under mild conditions. Highly controlled regio- and 1,2- cis-stereoselectivities were achieved via the combination of boron-mediated carbohydrate recognition and the Si-type mechanism. Mechanistic studies using the KIEs and DFT calculations were consistent with a highly dissociative concerted Si mechanism. This glycosylation method was applied successfully to the direct glycosylation of unprotected natural glycosides and the efficient synthesis of a complex oligosaccharide with minimal protecting groups.