Natural and engineered cyclodipeptides:Biosynthesis,chemical diversity,and engineering strategies for diversification and high-yield bioproduction.

Cyclodipeptides are diverse chemical scaffolds that show a broad range of bioactivities relevant for medicine,agriculture,chemical catalysis,and material sciences.Cyclodipeptides can be synthesized enzymatically through two unrelated enzyme families,non-ribosomal peptide synthetases(NRPS)and cyclodipeptide synthases(CDPSs).The chemical diversity of cyclodipeptides is derived from the two amino acid side chains and the modification of those side-chains by cyclodipeptide tailoring enzymes.While a large spectrum of chemical diversity is already known today,additional chemical space-and as such potential new bioactivities-could be accessed by exploring yet undiscovered NRPS and CDPS gene clusters as well as via engineering.Further,to exploit cyclodipeptides for applications,the low yield of natural biosynthesis needs to be overcome.In this review we summarize current knowledge on NRPS and CDPS-based cyclodipeptide biosynthesis,engineering approaches to further diversity the natural chemical diversity as well as strategies for high-yield production of cyclodipeptides,including a discussion of how advancements in synthetic biology and metabolic engineering can accelerate the translational potential of cyclodipeptides.

多粘类芽孢杆菌及其脂肽化合物研究进展

芽孢杆菌(Bacillus spp.)和类芽孢杆菌(Paenibacillus spp.)可产生丰富的代谢化合物,尤其是拮抗微生物类的脂肽化合物,是挖掘天然抗菌素的宝库,其中多粘类芽孢杆菌Paenibacillus polymyxa最具有代表性。多粘类芽孢杆菌的生防机制与其脂肽化合物相关。已发现与微生物拮抗作用相关的脂肽主要有杀镰孢菌素、多粘菌素和十三肽素,是由大的多酶复合体非核糖体肽合成酶(NRPSs)产生。本文在简介多粘类芽孢杆菌脂肽在植物病害防治和医疗应用的基础上,综述了其产生的脂肽化合物的类型和功能,并结合作者的研究工作,重点介绍了与抗菌作用相关的杀镰孢菌素、多粘菌素和十三肽素化合物的结构、生物活性、作用机制、类似物的合成和质谱检测等方面的研究进展,并展望了该领域的未来研究发展趋势,旨在为进一步发现、挖掘和利用脂肽化合物的自然资源提供参考。