文献类型：期刊文献

英文题名：AdpAlin regulates lincomycin and melanin biosynthesis by modulating precursors flux in Streptomyces lincolnensis

作者：Kang, Yajing[1];Wu, Wei[1];Zhang, Feixue[1];Chen, Lei[1];Wang, Ruida[1,2];Ye, Jiang[1,2,3];Wu, Haizhen[1,2,3];Zhang, Huizhan[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Dept Appl Biol, Shanghai, Peoples R China;[3]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2023

卷号：63

期号：6

起止页码：622

外文期刊名：JOURNAL OF BASIC MICROBIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000922615000001)】；

基金：ACKNOWLEDGMENTS This work was funded by the National Key Research and Development Program of China (2021YFC2100600).

语种：英文

外文关键词：AdpA; lincomycin; melanin; transcriptional regulation; tyrosine oxidases

摘要：Lincomycin is one of the most important antibiotics. However, transcriptional regulation network of secondary metabolism in Streptomyces lincolnensis, the lincomycin producer, remained obscure. AdpA from S. lincolnensis (namely AdpA(lin)) has been proved to activate lincomycin biosynthesis. Here we found that both lincomycin and melanin took l-tyrosine as precursor, and AdpA(lin) activated melanin biosynthesis as well. Three tyrosinases, MelC2, MelD2, and MelE, and one tyrosine peroxygenase, LmbB2, participated in lincomycin and melanin biosynthesis in different ways. For melanin biosynthesis, MelC2 was the only key enzyme required. For lincomycin biosynthesis, MelD2 and LmbB2 were positive factors and were suggested to convert l-tyrosine to l-dihydroxyphenylalanine (l-DOPA). Otherwise, MelC2 and MelE were negative factors for lincomycin biosynthesis and they were supposed to oxidize l-DOPA to generate melanin and certain unknown metabolite, respectively. Based on in silico analysis combined with electrophoretic mobility shift assays (EMSAs), we proved that AdpA(lin) directly interacted with promoters of melC, melD, and melE by binding to putative AdpA-binding sites in vitro. Moreover, in vivo experiments revealed that AdpA(lin) positively regulated the transcription of melC and melE, but negatively regulated melD. In conclusion, AdpA(lin) was the switch of secondary metabolism in S. lincolnensis, and it modulated precursor flux of lincomycin and melanin biosynthesis by directly activating melC, melE, and lmbB1/lmbB2 or repressing melD.