PMID- 33258169
OWN - NLM
STAT- MEDLINE
DCOM- 20210720
LR  - 20210720
IS  - 1521-3773 (Electronic)
IS  - 1433-7851 (Linking)
VI  - 60
IP  - 10
DP  - 2021 Mar 1
TI  - A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient 
      Production of Valuable Steroid Precursors.
PG  - 5414-5420
LID - 10.1002/anie.202015462 [doi]
AB  - 4-Androstenedione (4-AD) and progesterone (PG) are two of the most important 
      precursors for synthesis of steroid drugs, however their current manufacturing 
      processes suffer from low efficiency and severe environmental issues. In this 
      study, we decipher a dual-role reductase (mnOpccR) in the phytosterols 
      catabolism, which engages in two different metabolic branches to produce the key 
      intermediate 20-hydroxymethyl pregn-4-ene-3-one (4-HBC) through a 4-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. Inactivation or 
      overexpression of mnOpccR in the Mycobacterium neoaurum can achieve exclusive 
      production of either 4-AD or 4-HBC from phytosterols. By utilizing a two-step 
      synthesis, 4-HBC can be efficiently converted into PG in a scalable manner (100 
      gram scale). This study deciphers a pivotal biosynthetic mechanism of phytosterol 
      catabolism and provides very efficient production routes of 4-AD and PG.
CI  - (c) 2020 Wiley-VCH GmbH.
FAU - Peng, Haidong
AU  - Peng H
AD  - Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of 
      Education, School of Pharmaceutical Sciences, Wuhan University, 1 Luojiashan Rd., 
      Wuhan, 430071, China.
AD  - State Key Laboratory of Microbial Metabolism and School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai, 
      200240, China.
FAU - Wang, Yaya
AU  - Wang Y
AD  - Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of 
      Education, School of Pharmaceutical Sciences, Wuhan University, 1 Luojiashan Rd., 
      Wuhan, 430071, China.
FAU - Jiang, Kai
AU  - Jiang K
AD  - Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of 
      Education, School of Pharmaceutical Sciences, Wuhan University, 1 Luojiashan Rd., 
      Wuhan, 430071, China.
FAU - Chen, Xinru
AU  - Chen X
AD  - Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of 
      Education, School of Pharmaceutical Sciences, Wuhan University, 1 Luojiashan Rd., 
      Wuhan, 430071, China.
FAU - Zhang, Wenlu
AU  - Zhang W
AD  - Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of 
      Education, School of Pharmaceutical Sciences, Wuhan University, 1 Luojiashan Rd., 
      Wuhan, 430071, China.
FAU - Zhang, Yanan
AU  - Zhang Y
AD  - Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of 
      Education, School of Pharmaceutical Sciences, Wuhan University, 1 Luojiashan Rd., 
      Wuhan, 430071, China.
FAU - Deng, Zixin
AU  - Deng Z
AD  - Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of 
      Education, School of Pharmaceutical Sciences, Wuhan University, 1 Luojiashan Rd., 
      Wuhan, 430071, China.
AD  - State Key Laboratory of Microbial Metabolism and School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai, 
      200240, China.
FAU - Qu, Xudong
AU  - Qu X
AUID- ORCID: 0000-0002-3301-8536
AD  - Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of 
      Education, School of Pharmaceutical Sciences, Wuhan University, 1 Luojiashan Rd., 
      Wuhan, 430071, China.
AD  - State Key Laboratory of Microbial Metabolism and School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai, 
      200240, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210119
PL  - Germany
TA  - Angew Chem Int Ed Engl
JT  - Angewandte Chemie (International ed. in English)
JID - 0370543
RN  - 0 (Bacterial Proteins)
RN  - 0 (Phytosterols)
RN  - 0 (Pregnenes)
RN  - 409J2J96VR (Androstenedione)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 1.- (Oxidoreductases)
RN  - Mycolicibacterium neoaurum
SB  - IM
MH  - Androstenedione/chemical synthesis
MH  - Bacterial Proteins/genetics/*metabolism
MH  - Biocatalysis
MH  - Mycobacteriaceae/enzymology/genetics
MH  - Oxidoreductases/genetics/*metabolism
MH  - Phytosterols/*metabolism
MH  - Pregnenes/chemistry/*metabolism
MH  - Progesterone/chemical synthesis
OTO - NOTNLM
OT  - acyl-CoA reductase
OT  - biosynthesis
OT  - biosynthetic pathway
OT  - semi-synthesis
OT  - steroids
EDAT- 2020/12/02 06:00
MHDA- 2021/07/21 06:00
CRDT- 2020/12/01 06:04
PHST- 2020/11/19 00:00 [received]
PHST- 2020/12/02 06:00 [pubmed]
PHST- 2021/07/21 06:00 [medline]
PHST- 2020/12/01 06:04 [entrez]
AID - 10.1002/anie.202015462 [doi]
PST - ppublish
SO  - Angew Chem Int Ed Engl. 2021 Mar 1;60(10):5414-5420. doi: 10.1002/anie.202015462. 
      Epub 2021 Jan 19.