摘要
越野他汀(kosinostatin,KST)产生菌小单孢菌TP-A0468菌株基因组中包含了负责产生越野他汀、利福霉素等多种次级代谢产物的生物合成基因簇.在越野他汀生物合成研究中,从越野他汀生物合成基因簇中腺苷酰化酶基因kst B1的缺失突变株小单孢菌TP-A0468Δkst B1中分离到了新蒽环化合物554B.经质谱和核磁共振鉴定,其糖基部分是4-乙酰基-2,3,6-三脱氧己糖,而非越野他汀中的4-乙酰基-2,6-二脱氧己糖,表明其生物合成过程中发生了一步额外的3,4-脱水反应.然而KST生物合成基因簇中并不包含相应的己糖3,4-脱水酶基因.通过对基因组序列进行生物信息学分析,在利福霉素生物合成基因簇中发现了一个编码己糖3,4-脱水酶的基因orf6.基因删除实验显示orf6失活的突变株不再产生554B,表明该基因与4-乙酰基-2,3,6-三脱氧己糖的生物合成相关.结果表明小单孢菌TP-A0468可以利用不同生物合成基因簇中的基因协同介导天然产物的生物合成.
Micromonospora sp. TP-A0468 harbors multiple biosynthetic gene clusters encoding the biosynthesis of secondary metabolites, including kosinostatin（KST） and rifamycins. In our study on the biosynthesis of KST, a new anthracycline polyketide 554 B was isolated from the kst B1 deletion mutant Δkst B1 and identified as shunt product of KST pathway bearing 4-acetyl-2,3,6-deoxyhexosyl moiety. The unexpected elimination of C-3＇ hydroxyl suggests a 3,4-dehydratase involved in the biosynthesis of 554 B, of which the encoding gene was proposed to located beyond the kst gene cluster. Bioinformatic analysis revealed orf6 of rifamycin biosynthetic gene cluster（rif） was the candidate of required 3,4-dehydratase gene. Deletion of orf6 abolished the production of 554 B, confirming the involvement of orf6 in the biosynthesis of 554 B. Our study attributed orf6 to the origin of 2,3,6-deoxyhexosyl and unveiled the cooperation between biosynthetic gene clusters in Micromonospora sp. TP-A0468.
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2017年第12期3262-3266,共5页
Chinese Journal of Organic Chemistry
基金
国家自然科学基金(No.81373307)
上海市科学技术委员会(No.14XD1404500)资助项目~~
