Progesterone from 3-Acetoxybisnor-5-cholenaldehyde and 3-Ketobisnor-4-cholenaldehyde

Heyl, Frederick W.; Herr, Milton E.

doi:10.1021/ja01162a076

“…Activity assays reveal that these two mutants lose activity on 3-OPC-CoA (10), but retain activity to efficiently reduce the aldehyde 3-OPA(9)(Figure 4, trace VI to IX). This confirms that the NtD is responsible for the conversion of aldehyde to alcohol and the CtD appears to catalyze the reduction of 3-OPC-CoA (10)t oa ldehyde.I n addition, the 3-OPA (9)was not able to be detected during the reduction of 3-OPC-CoA (10), suggesting that this aldehyde intermediate was shuttled within an internal tunnel between the N-and C-terminal domains.…”

Section: Deciphering the Catalytic Mechanism Of Mnopccrmentioning

confidence: 93%

A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient Production of Valuable Steroid Precursors

Peng

¹

,

Wang

²

,

Jiang

³

et al. 2021

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4-Androstenedione (4-AD) and progesterone (PG) are two of the most important precursors for synthesis of steroid drugs,h owever their current manufacturing processes suffer from low efficiency and severe environmental issues.In this study,wedecipher adual-role reductase (mnOpccR) in the phytosterols catabolism, whiche ngages in two different metabolic branches to produce the key intermediate 20hydroxymethyl pregn-4-ene-3-one (4-HBC) through a4-e reduction of 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA) and 2-e reduction of 3-oxo-4-pregnene-20-carboxyl aldehyde (3-OPA), respectively.I nactivation or overexpression of mnOpccR in the Mycobacterium neoaurum can achieve exclusive production of either 4-AD or 4-HBC from phytosterols.B yu tilizing at wo-step synthesis,4-HBC can be efficiently converted into PG in as calable manner (100 gram scale). This study deciphers ap ivotal biosynthetic mechanism of phytosterol catabolism and provides very efficient production routes of 4-AD and PG.

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“…Synthesis of PG from 4‐HBC has been previously documented [9–11] . The synthetic procedure contains two separate steps; the conversion of 4‐HBC to 4‐HBC aldehyde, and the conversion of the aldehyde to PG.…”

Section: Resultsmentioning

confidence: 99%

“…With the objective of improving the production of 4-HBC, we first replicated the reported strategy in ATCC 25795 to delete hsd4A in mJTU1,g enerating the strain mJTU2. [12] Blocking the conversion of 22-OH-BNC-CoA (7)t o2 2-oxo-BNC-CoA (8)was assumed to direct 7 into entering the retroaldol elimination route.Subsequently,this would yield 3-oxo-4-pregnene-20-aldehyde 9), leading to the conversion of 4-HBC by aldehyde reductase (Figure 1). However, our experimental results of hsd4A deletion (97.4 %identity to the Hsd4A in ATCC 25795), show no effect on the profile of products (Figure 2, trace II-III).…”

Section: Unveiling 3-opc-coa Reduction Involves the Formation Of 4-hbc And Inactivation Of Chse1-e2 And Chsh1-h2 To Produce 3-opc And 3-omentioning

confidence: 99%

A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient Production of Valuable Steroid Precursors

Peng

¹

,

Wang

²

,

Jiang

³

et al. 2021

View full text Add to dashboard Cite

4-Androstenedione (4-AD) and progesterone (PG) are two of the most important precursors for synthesis of steroid drugs,h owever their current manufacturing processes suffer from low efficiency and severe environmental issues.In this study,wedecipher adual-role reductase (mnOpccR) in the phytosterols catabolism, whiche ngages in two different metabolic branches to produce the key intermediate 20hydroxymethyl pregn-4-ene-3-one (4-HBC) through a4-e reduction of 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA) and 2-e reduction of 3-oxo-4-pregnene-20-carboxyl aldehyde (3-OPA), respectively.I nactivation or overexpression of mnOpccR in the Mycobacterium neoaurum can achieve exclusive production of either 4-AD or 4-HBC from phytosterols.B yu tilizing at wo-step synthesis,4-HBC can be efficiently converted into PG in as calable manner (100 gram scale). This study deciphers ap ivotal biosynthetic mechanism of phytosterol catabolism and provides very efficient production routes of 4-AD and PG.

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“…comparison with published data suggested that acetone may have been incorporated into the crystal lattice of the original product. 3 The IR, MS, NMR and crystallographic data for (2) have not been published previously.…”

Section: Discussionmentioning

confidence: 99%

“…3-Oxo-23,24-dinorchol-4-ene-22-cyanohydrin (2) was synthesised from 3-oxo-23,24-dinorchol-4-ene-22-al (1) using a method different from that described by Heyl and Herr. 3 Its crystal structure was determined (see Fig. 1).…”

mentioning

confidence: 99%

Synthesis and X-ray Crystal Structure of 3-oxo-23, 24-Dinorchol-4-Ene-22-Cyanohydrin

Cox

¹

,

Nahar

²

,

Sarker

³

et al. 2004

Journal of Chemical Research

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Progesterone from 3-Acetoxybisnor-5-cholenaldehyde and 3-Ketobisnor-4-cholenaldehyde

Cited by 32 publications

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A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient Production of Valuable Steroid Precursors

A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient Production of Valuable Steroid Precursors

A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient Production of Valuable Steroid Precursors

Synthesis and X-ray Crystal Structure of 3-oxo-23, 24-Dinorchol-4-Ene-22-Cyanohydrin

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