Flavoenzyme CrmK-mediated substrate recycling in caerulomycin biosynthesis
Zhu, Yiguang; Picard, Marie-Eve; Zhang, Qingbo; Barma, Julie; Despres, Xavier Murphy; Mei, Xiangui; Zhang, Liping; Duvignaud, Jean-Baptiste; Couture, Manon; Zhu, Weiming; Shi, Rong; Zhang, Changsheng; Zhang, CS (reprint author), Chinese Acad Sci, South China Sea Inst Oceanol, Guangdong Key Lab Marine Mat Med, CAS Key Lab Trop Marine Bioresources & Ecol, 164 West Xingang Rd, Guangzhou 510301, Guangdong, Peoples R China.; Shi, R (reprint author), Univ Laval, IBIS, PROTEO, Dept Biochim Microbiol & Bioinformat, Ville De Quebec, PQ G1V 0A6, Canada.
2016
发表期刊CHEMICAL SCIENCE
卷号7期号:8页码:4867-4874
摘要Substrate salvage or recycling is common and important for primary metabolism in cells but is rare in secondary metabolism. Herein we report flavoenzyme CrmK-mediated shunt product recycling in the biosynthesis of caerulomycin A (CRM A 1), a 2,2'-bipyridine-containing natural product that is under development as a potent novel immunosuppressive agent. We demonstrated that the alcohol oxidase CrmK, belonging to the family of bicovalent FAD-binding flavoproteins, catalyzed the conversion of an alcohol into a carboxylate via an aldehyde. The CrmK-mediated reactions were not en route to 1 biosynthesis but played an unexpectedly important role by recycling shunt products back to the main pathway of 1. Crystal structures and site-directed mutagenesis studies uncovered key residues for FAD-binding, substrate binding and catalytic activities, enabling the proposal for the CrmK catalytic mechanism. This study provides the first biochemical and structural evidence for flavoenzyme-mediated substrate recycling in secondary metabolism.
部门归属[Zhu, Yiguang; Zhang, Qingbo; Zhang, Liping; Zhang, Changsheng] Chinese Acad Sci, South China Sea Inst Oceanol, Guangdong Key Lab Marine Mat Med, CAS Key Lab Trop Marine Bioresources & Ecol, 164 West Xingang Rd, Guangzhou 510301, Guangdong, Peoples R China; [Picard, Marie-Eve; Barma, Julie; Despres, Xavier Murphy; Duvignaud, Jean-Baptiste; Couture, Manon; Shi, Rong] Univ Laval, IBIS, PROTEO, Dept Biochim Microbiol & Bioinformat, Ville De Quebec, PQ G1V 0A6, Canada; [Mei, Xiangui; Zhu, Weiming] Ocean Univ China, Sch Med & Pharm, Chinese Minist Educ, Key Lab Marine Drugs, 5 Yushan Rd, Qingdao 266003, Peoples R China ; LMB
学科领域Chemistry
文献类型期刊论文
条目标识符http://ir.scsio.ac.cn/handle/344004/15519
专题中科院海洋生物资源可持续利用重点实验室
通讯作者Zhang, CS (reprint author), Chinese Acad Sci, South China Sea Inst Oceanol, Guangdong Key Lab Marine Mat Med, CAS Key Lab Trop Marine Bioresources & Ecol, 164 West Xingang Rd, Guangzhou 510301, Guangdong, Peoples R China.; Shi, R (reprint author), Univ Laval, IBIS, PROTEO, Dept Biochim Microbiol & Bioinformat, Ville De Quebec, PQ G1V 0A6, Canada.
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Zhu, Yiguang,Picard, Marie-Eve,Zhang, Qingbo,et al. Flavoenzyme CrmK-mediated substrate recycling in caerulomycin biosynthesis[J]. CHEMICAL SCIENCE,2016,7(8):4867-4874.
APA Zhu, Yiguang.,Picard, Marie-Eve.,Zhang, Qingbo.,Barma, Julie.,Despres, Xavier Murphy.,...&Shi, R .(2016).Flavoenzyme CrmK-mediated substrate recycling in caerulomycin biosynthesis.CHEMICAL SCIENCE,7(8),4867-4874.
MLA Zhu, Yiguang,et al."Flavoenzyme CrmK-mediated substrate recycling in caerulomycin biosynthesis".CHEMICAL SCIENCE 7.8(2016):4867-4874.
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