Deletion of COM donor and acceptor domains and the interaction between modules in bacillomycin D produced by Bacillus amyloliquefaciens  

作　　者：Ziyan Lv Wenjie Ma Ping Zhang Zhaoxin Lu Libang Zhou Fanqiang Meng Zuwei Wang Xiaomei Bie 

机构地区：[1]Nanjing Agricultural University,College of Food Science and Technology,Nanjing,210095,China

出　　处：《Synthetic and Systems Biotechnology》2022年第3期989-1001,共13页合成和系统生物技术（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(grant no.31972174).

摘　　要：Bacillomycin D is a cyclic lipopeptide produced by Bacillus amyloliquefaciens fmbJ.At present,no relevant report has described the combinatorial biosynthesis of bacillomycin D.Due to the strong biosynthetic potential of the communication-mediating(COM)domains,its crosstalk between NRPS subunits has been studied to some extent,but the interaction of COM domain between modules is rarely reported.Therefore,in this study,we conducted the combinatorial biosynthesis of bacillomycin D through the deletion of the COM donor and acceptor domains between the modules and elucidated the interaction between the NRPS modules.The results showed that the deletion of the donor domain between modules 2 and 3 did not affect catalysis by upstream modules,but prevented downstream modules from catalysing the extension of the lipopeptide product,ultimately resulting in mutant complexes that could form linear dipeptides with the sequenceβ-NH_(2)FA-Asn-Tyr.However,the engineered hybrid bacillomycin D NRPSs lacking the donor domains between modules 3 and 4 and modules 6 and 7 could form multiple assembly lines that produced bacillomycin D and its analogs(linear tripeptides,cyclic hexapeptides and linear hexapeptides).In addition,all the acceptor domain deletion strains failed to produce bacillomycin D,only truncated peptides produced by module interruption(except for the acceptor domain deletion strains between modules 3 and 4,which also produced cyclic hexapeptides).In conclusion,deletion of the inter-module donor domains led to a more flexible hybrid biosynthetic system for the production of diverse peptide products;compared with the inter-subunit donor domain deletion strains that could only produce truncated peptides,the former had a greater biosynthetic capacity.Meanwhile,the acceptor domains between modules were an important part of module-module interactions and efficient communication within bacillomycin D synthetase.

关 键 词：Bacillomycin D COM domain Interaction between modules Lipopeptide analogs 

分 类 号：O15[理学—数学]