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Targeted genome mining for microbial antitumor agents acting through DNA intercalation
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作者 Zhijie Zhao Guiyun Zhao +7 位作者 Yi Chai Wei Li Kaihui Song Wenbin Zhao Hairong Li Miaolian Wu Zhan Zhou yi-ling du 《Synthetic and Systems Biotechnology》 SCIE CSCD 2023年第3期520-526,共7页
Microbial natural products have been one of the most important sources for drug development.In the current postgenomic era,sequence-driven approaches for natural product discovery are becoming increasingly popular.Her... Microbial natural products have been one of the most important sources for drug development.In the current postgenomic era,sequence-driven approaches for natural product discovery are becoming increasingly popular.Here,we develop an effective genome mining strategy for the targeted discovery of microbial metabolites with antitumor activities.Our method employs uvrA-like genes as genetic markers,which have been identified in the biosynthetic gene clusters(BGCs)of several chemotherapeutic drugs of microbial origin and confer self-resistance to the corresponding producers.Through systematic genomic analysis of gifted actinobacteria genera,identification of uvrA-like gene-containing BGCs,and targeted isolation of products from a BGC prioritized for metabolic analysis,we identified a new tetracycline-type DNA intercalator timmycins.Our results thus provide a new genome mining strategy for the efficient discovery of antitumor agents acting through DNA intercalation. 展开更多
关键词 Genome mining Microbial natural product DNA intercalator UvrA-like protein Biosynthetic gene clusters TETRACYCLINE
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Rational and semi-rational engineering of cytochrome P450s for biotechnological applications 被引量:4
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作者 Lian-Hua Xu yi-ling du 《Synthetic and Systems Biotechnology》 SCIE 2018年第4期283-290,共8页
The cytochrome P450 enzymes are ubiquitous heme-thiolate proteins performing regioselective and stereoselective oxygenation reactions in cellular metabolism.Due to their broad substrate scope and catalytic versatility... The cytochrome P450 enzymes are ubiquitous heme-thiolate proteins performing regioselective and stereoselective oxygenation reactions in cellular metabolism.Due to their broad substrate scope and catalytic versatility,P450 enzymes are also attractive candidates for many industrial and biopharmaceutical applications.For particular uses,enzyme properties of P450s can be further optimized through directed evolution,rational,and semi-rational engineering approaches,all of which introduce mutations within the P450 structures.In this review,we describe the recent applications of these P450 engineering approaches and highlight the key regions and residues that have been identified using such approaches.These“hotspots”lie within critical functional areas of the P450 structure,including the active site,the substrate access channel,and the redox partner interaction interface. 展开更多
关键词 Cytochrome P450 Protein engineering Rational design Crystal structure
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