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

• -stage enzymatic functionalization of core scaffolds could be effective. Selectivity towards target biomolecules can be tailored by gradually increasing the oxidation level of the complex scaffold or by further site- and stereoselective modifications. Through rational enzyme engineering, the selectivity

• regio- and diastereocontrolled hydroxylation at C3, along with transposition of the double bond, to form the desired product 22 in approximately 20% yield with 50% conversion. To enhance efficiency of the enzymatic oxidation, Renata and co-workers conducted two approaches: homolog screening and enzyme

• engineering. A Genome Neighborhood Diagram (GND) analysis [26] of dioxygenase Bsc9 identified five homologs, including a homolog MoBsc9 derived from Magnaporthe oryzae, which shares 54% sequence identity with Bsc9 and was found to be suitable for the oxidative allylic rearrangement (21→22). Further directed

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• enzyme engineering and rational design [73][74]. Lentzea kentuckyensis sp. produces lassomycin (Figure 4), a lasso peptide, with a methyl ester at the C-terminus. The las cluster encodes LasF, which is predicted to function as an O-MT. Since no other putative MT is encoded in the las cluster, LasF is

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• efficiency of synthetic approaches, have already shown a growing influence in the synthesis of bioactive natural products, pharmaceutical components, and other valuable molecules with the development of microbial genetics and enzyme engineering [19][20][21][22]. The comprehensive investigation of TE domains

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• for the design of biosynthetic machineries to produce a variety of bioactive meroterpenoids. Keywords: αKG-dependent dioxygenases; enzyme engineering; fungal meroterpenoids; synthetic biology; terpene cyclases; Introduction Meroterpenoids are complex natural products with intricate skeletal

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• reactions (Figure S1, Supporting Information File 1). Due to the high reaction selectivity that the enzyme active site offers, these enzymes provide biocatalytic means for the biaryl linkage formation, and recent enzyme engineering efforts also demonstrated selective and efficient production of unnatural

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• engineering strategies in the light of the newly emerging structural information on megasynthases, and argue that fatty acid synthases (FAS) are and will be valuable objects for further developing this field. Keywords: fatty acid synthases; megasynthases; metabolic enzyme engineering; polyketide synthases

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• terpene producing Escherichia coli, this review shall give an insight in recent progresses regarding manipulation of mostly diterpene synthases. Keywords: enzyme engineering; heterologous production in E. coli; metabolic pathway optimization; modular biosynthesis; plant diterpenes; Introduction

• feedback inhibition loops. Heterologous production of several diterpenes could already be realized in stable systems with moderate yields, validating the established approaches of enzyme engineering for terpene synthases. Yet this success could not be transferred in full extend to heterologous expression

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• a tryptophan residue modified with an isoprenyl group is not always restricted to a location near the C-terminal end. The broad substrate tolerance of the modifying enzyme ComQ may attract attention as an enzyme engineering target for the synthesis of prenylated tryptophan derivatives. However

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• from Thermotoga neapolitana [22]. However, two main problems still exist for the AI-catalyzed D-tagatose synthesis. The catalytic efficiency of AI for D-galactose is relatively low compared to its natural substrate L-arabinose. Enzyme engineering has thus been reported to improve the efficiency of AI