Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• this problem, the research group designed synthetic substrate analogs (96, 101) that mimic the biosynthetic intermediate 88 (Scheme 10A). By replacing an amide linkage in 88 with an ester linkage, the fatty acid side chain could be removed under mild conditions after enzymatic construction of the

• chemo-enzymatic total synthesis was the strategic focus on peptidyl aldehyde 88, the intermediate that transiently dissociates from the enzymes in the biosynthetic pathway. Leveraging the broad substrate tolerance of SfmC towards 88 facilitated the design of substrate analogs that streamlined enzymatic

• novel paradigm for exploiting the inherent specificity and efficiency of enzymatic catalysts within synthetic sequences. The integration of designed substrate analogs that can be transformed by promiscuous enzymes provides a versatile synthetic platform towards natural products and their derivatives. In

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• combinatorial biosynthesis. An important review published previously comprehensively addressed the transformation of synthetic prenyl-substrate analogs by TSs as well as TS-mimicking chemical transformations [13]. In this review, we discuss representative MSTSs originating from different species that use

• analogs have been synthesized to act as actual substrates of TSs to generate novel terpene skeletons, introduce reaction handles, and produce value-added compounds. A previous review has covered the advances of TS-catalyzed transformations of synthetic substrate analogs up to 2019 [13][42]. Here, we

Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• of the 2-methylisoborneol synthase was investigated through enzyme incubations with several substrate analogs, giving access to two C12 monoterpenoids. Implications on the stereochemical course of the terpene cyclisation by 2-methylisoborneol synthase are discussed. Keywords: biosynthesis; enzymes

• ; isotopes; substrate analogs; terpenes; Introduction The musty odorant 2-methylisoborneol (1, Scheme 1) has first been obtained through synthesis from camphor [1] and has subsequently been discovered as a natural product in streptomycetes [2][3]. The volatile compound was later also found in various other

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• be obtained via feeding the engineered strain with substrate analogs. This integration of multiple strategies highlights the great potential of synthetic biology for the production of valuable complex terpenoids [157]. Conclusion Despite the ubiquitous distribution of terpene biosynthetic pathways in

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• detailed information on the activity of a given enzyme with different substrate analogs. Besides providing the necessary information to identify interesting enzyme candidates for level 4 and level 5 pathway construction, more systematic data on enzyme promiscuity would also allow a more holistic view onto