A wide range of perylenequinones (PQs) with diverse structures and versatile bioactivities have long been isolated, positioning them as highly promising agents for photodynamic therapy (PDT). However, the lack of an efficient and cost-effective method to obtain these compounds and to introduce structural diversity and complexity currently hinders their further research and application. In this concept, we present a comprehensive overview of the advancements in the biosynthetic pathways of natural PQs based on their structural classification, and also summarize recent progress in the biosynthesis of natural PQs and derivatives. These pioneering efforts may pave the way for structure modification and large-scale bioproduction of natural and unnatural PQs through synthetic biology strategies to promote their drug development.
Abstract Plant-derived alkaloids are an important class of pharmaceuticals. However, they still rely on phytoextraction to meet their diverse market demands. Since multistep biocatalytic cascades have begun to revolutionize the manufacture of natural or unnatural products, to address the synthetic challenges of alkaloids, herein we establish an artificially concise four-enzyme biocatalytic cascade with avoiding plant-derived P450 modification for synthesizing phenethylisoquinoline alkaloids (PEIAs) after enzyme discovery and enzyme engineering. Efficient biosynthesis of diverse natural and unnatural PEIAs is realized from readily available substrates. Most importantly, the scale-up preparation of the colchicine precursor ( S )-autumnaline with a high titer is achieved after replacing the rate-limiting O -methylation by the plug-and-play strategy. This study not only streamlines future engineering endeavors for colchicine biosynthesis, but also provides a paradigm for constructing more artificial biocatalytic cascades for the manufacture of diverse alkaloids through synthetic biology.
Abstract An unprecedented [4+2] cycloaddition of in situ generated azoalkenes with arylacetic acids has been developed under the catalysis of isothiourea. The reaction provided an efficient approach to the synthesis of 4,5‐dihydropyridazin‐3(2 H )‐one derivatives in moderate to good yields (up to 95%). magnified image
Naturally-occurring Emodin was successfully employed in the selective oxidation of sulfides promoted by visible-light as a novel organic photocatalyst for the first time.
Abstract New‐to‐nature biocatalysis in organic synthesis has recently emerged as a green and powerful strategy for the preparation of valuable chiral products, among which chiral oxygen‐containing benzo‐fused heterocycles are important structural motifs in pharmaceutical industry. However, the asymmetric synthesis of these compounds through radical‐mediated methods is challenging. Herein, a novel asymmetric radical‐mediated photoenzymatic synthesis strategy is developed to realize the efficient enantioselective synthesis of oxygen‐containing benzo‐fused heterocycles through structure‐guided engineering of a flavin‐dependent ‘ene’‐reductase GluER. It shows that variant GluER‐W100H could efficiently produce various benzoxepinones, chromanone and indanone with different benzo‐fused rings in high yields with great stereoselectivities under visible light. Moreover, these results are well supported by mechanistic experiments, revealing that this photoenzymatic process involves electron donor‐acceptor complex formation, single electron transfer and hydrogen atom transfer. Therefore, we provide an alternative green approach for efficient chemoenzymatic synthesis of important chiral skeletons of bioactive pharmaceuticals.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
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