Genomics-driven discovery of pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis
作者单位：Fundación MEDINACentro de Excelencia en Investigación de Medicamentos Innovadores en AndaluciaGranadaSpain Brown Foundation Institute of Molecular MedicineUniversity of Texas Health Science Center at HoustonHoustonTX 77030USA
会议名称：《2012年中国菌物学会学术年会》
会议日期：2012年
学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学]
关 键 词：Caspofungin pneumocandin Glarea lozoyensis genome gene cluster
摘 要：The antifungal caspofungin is a semi-synthetic derivative of the lipohexapetide pneumocandin B produced by the fungus Glarea lozoyensis.A whole genome sequencing approach has identified the pneumocandin biosynthetic gene cluster which contains a nonribosomal peptide synthetase(NRPS,GLNRPS4),a polyketide synthase(PKS,GLPKS4),and at least nine other modifying *** mutants of GLNRPS4 or GLPKS4 no longer produce pneumocandin and lose their antibiotic activity against Candida *** additional to pneumocandins,the *** genome reveals a rich repertoire of natural product-encoding gene clusters which include 24 PKSs,6 NRPSs,5 PKS-NRPS hybrids,2 dimethylallyltryptophan synthases,and 3 terpene *** of the gene cluster provides a blueprint for bioengineering novel pneumocandin derivatives with more desirable pharmacological properties such as oral *** genome estimation of secondary metabolite-encoding genes from *** illustrates the huge potential for natural products drug discovery from the vast fungal kingdom.