Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, USA.
Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
Nat Prod Rep. 2016 Feb;33(2):348-64. doi: 10.1039/c5np00097a.
Cyanobacteria are a prolific source of structurally unique and biologically active natural products that derive from intriguing biochemical pathways. Advancements in genome sequencing have accelerated the identification of unique modular biosynthetic gene clusters in cyanobacteria and reveal a wealth of unusual enzymatic reactions involved in their construction. This article examines several interesting mechanistic transformations involved in cyanobacterial secondary metabolite biosynthesis with a particular focus on marine derived modular polyketide synthases (PKS), nonribosomal peptide synthetases (NRPS) and combinations thereof to form hybrid natural products. Further, we focus on the cyanobacterial genus Moorea and the co-evolution of its enzyme cassettes that create metabolic diversity. Progress in the development of heterologous expression systems for cyanobacterial gene clusters along with chemoenzymatic synthesis makes it possible to create new analogs. Additionally, phylum-wide genome sequencing projects have enhanced the discovery rate of new natural products and their distinctive enzymatic reactions. Summarizing, cyanobacterial biosynthetic gene clusters encode for a large toolbox of novel enzymes that catalyze unique chemical reactions, some of which may be useful in synthetic biology.
蓝藻是结构独特且具有生物活性的天然产物的丰富来源,这些天然产物源自有趣的生化途径。基因组测序的进步加速了蓝藻中独特模块化生物合成基因簇的鉴定,并揭示了大量参与其构建的不寻常的酶促反应。本文探讨了蓝藻次生代谢物生物合成中涉及的几种有趣的机制转化,特别关注海洋衍生的模块化聚酮合酶(PKS)、非核糖体肽合酶(NRPS)及其组合形成的混合天然产物。此外,我们还关注蓝藻属 Moorea 及其酶盒的共同进化,这些酶盒创造了代谢多样性。蓝藻基因簇异源表达系统的发展以及化学酶合成使得创造新类似物成为可能。此外,门级全基因组测序项目提高了新天然产物及其独特酶促反应的发现率。总之,蓝藻生物合成基因簇编码了用于催化独特化学反应的大量新型酶,其中一些可能在合成生物学中有用。